Transcription Initiation: How RNA Polymerase Begins Gene Expression

By Dr. Zubair Khalid, DVM, MS, PhD · 2026-08-11

Key Takeaways

• Transcription initiation is the critical regulatory step where RNA polymerase binds to a promoter, unwinds DNA to form an "open complex," and synthesizes the first few RNA nucleotides, determining gene expression levels and conditions.
• In prokaryotes, the sigma (σ) factor directs the core RNA polymerase to promoter sequences (e.g., -10 TATAAT and -35 TTGACA boxes), enabling direct promoter recognition without ATP.
• Eukaryotic RNA polymerase II requires a preinitiation complex (PIC) assembled with general transcription factors (GTFs) like TFIID (containing TBP) and TFIIH, which unwinds DNA using ATP hydrolysis and phosphorylates the Pol II CTD for promoter escape.
• Abortive initiation, the repeated synthesis and release of short RNA transcripts (2-9 nt in bacteria), is a normal, regulated process preceding promoter escape, not an error, and its frequency is influenced by promoter strength and regulatory factors.
• Regulation of initiation involves sequence-specific DNA-binding proteins (activators and repressors), distal elements (enhancers and silencers), and epigenetic modifications (chromatin remodeling, histone acetylation/methylation, DNA methylation) that control promoter accessibility and PIC assembly.
• The phosphorylation state of the C-terminal domain (CTD) of eukaryotic Pol II, particularly serine 5 phosphorylation by TFIIH, is crucial for promoter escape and the recruitment of capping enzymes, linking initiation to downstream RNA processing.

Every gene, whether it encodes a metabolic enzyme in a bacterium or a signaling protein in a human neuron, must be read and converted into RNA before it can direct the synthesis of a protein. The process of copying a DNA sequence into RNA is called transcription, and it proceeds in three phases: initiation, elongation, and termination. Of these, initiation is the most consequential. It is the point at which the cell decides whether a gene will be expressed at all, how often it will be expressed, and under what conditions. Transcription initiation is the controlled gateway to gene expression, and understanding its mechanism is essential for understanding how cells respond to their environment, how development proceeds, and how misregulation leads to disease.

What Is Transcription Initiation?

Transcription initiation is the first phase of transcription, encompassing all the events from the initial recognition of a DNA sequence by RNA polymerase to the synthesis of the first few nucleotides of a new RNA transcript. It begins when RNA polymerase, the enzyme responsible for RNA synthesis, locates and binds to a specific DNA sequence called a promoter. It ends when the polymerase has successfully synthesized a short RNA product—typically 8 to 10 nucleotides in prokaryotes—and transitions into the elongation phase, during which it moves processively along the template strand, extending the RNA chain.

Initiation is not a single binding event but a multi-step process involving conformational changes in both the enzyme and the DNA. The polymerase must first bind to the promoter in a "closed" complex, in which the DNA remains double-stranded. It must then unwind a region of the DNA to expose the template strand, forming an "open" complex. Only after this unwinding can the polymerase begin to catalyze the formation of phosphodiester bonds between ribonucleotide triphosphates (NTPs), the building blocks of RNA.

The importance of initiation cannot be overstated. In most genes, the decision to transcribe is made at the level of initiation. Regulatory proteins that activate or repress gene expression almost always exert their effects by influencing the frequency or efficiency of initiation. Once RNA polymerase has escaped the promoter and entered elongation, the transcript is usually committed to completion. Thus, initiation is the primary control point for gene expression, and its regulation underlies processes as diverse as bacterial adaptation to new nutrients, the differentiation of stem cells into specialized cell types, and the aberrant proliferation of cancer cells.

The Players: RNA Polymerase and Promoters

RNA Polymerase

RNA polymerase is the enzyme that catalyzes the synthesis of RNA from a DNA template. It is a large, multi-subunit complex that reads the template strand of DNA in the 3′ to 5′ direction and synthesizes RNA in the 5′ to 3′ direction. Unlike DNA polymerase, RNA polymerase does not require a primer; it can initiate RNA synthesis de novo, using a single NTP as the first nucleotide.

In bacteria, there is a single core RNA polymerase enzyme, composed of five subunits: two copies of alpha (α), one beta (β), one beta-prime (β′), and one omega (ω). The core enzyme is catalytically active but cannot recognize promoters on its own. It requires an additional subunit called sigma (σ) factor, which associates with the core enzyme to form the holoenzyme. Sigma factor is responsible for promoter recognition; it dramatically reduces the affinity of RNA polymerase for non-specific DNA and directs the enzyme to specific promoter sequences. The most common sigma factor in Escherichia coli is σ70, which recognizes the consensus promoter sequences of most housekeeping genes. Alternative sigma factors, such as σ32 (heat shock) or σ54 (nitrogen metabolism), direct RNA polymerase to different sets of genes under specific stress conditions.

Eukaryotes are more complex. They possess three nuclear RNA polymerases: RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes; RNA polymerase II (Pol II), which transcribes all protein-coding genes and most non-coding RNA genes; and RNA polymerase III (Pol III), which transcribes transfer RNA (tRNA) genes and the 5S rRNA gene. Pol II is the most studied because it is responsible for messenger RNA (mRNA) synthesis. Pol II itself is a 12-subunit enzyme, but unlike bacterial RNA polymerase, it cannot recognize promoters or initiate transcription on its own. It requires a set of accessory proteins called general transcription factors (GTFs), which assemble at the promoter together with Pol II to form the preinitiation complex (PIC). The GTFs are named TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH (TFII stands for transcription factor for RNA polymerase II).

Promoter Sequences

A promoter is a DNA sequence located upstream of the transcription start site (TSS) that directs RNA polymerase to the correct position and determines the direction of transcription. Promoters are not transcribed themselves; they are recognition elements. Their sequences are not random—they contain conserved motifs that are recognized by specific proteins.

In bacteria, the promoter recognized by σ70-containing RNA polymerase holoenzyme contains two key conserved elements: the −10 box (also called the Pribnow box) and the −35 box. These names refer to their positions relative to the transcription start site, which is designated +1. The −10 box has the consensus sequence TATAAT, and the −35 box has the consensus sequence TTGACA. The sigma factor makes sequence-specific contacts with both boxes, positioning the polymerase so that its active site is approximately 10 base pairs downstream of the −10 box, at the start site. The spacing between the −10 and −35 boxes is typically 16 to 18 base pairs, and this spacing is critical; altering it by even one base pair can severely reduce promoter strength. Some promoters also contain an upstream element (UP element), an A/T-rich sequence located between −40 and −60, which is recognized by the α subunit of RNA polymerase and increases promoter strength.

In eukaryotes, the promoter for Pol II is more complex and modular. The core promoter is the minimal region required for accurate initiation by Pol II and the GTFs. It typically spans from about −40 to +40 relative to the TSS and contains one or more of the following elements: the TATA box, the initiator (Inr), the downstream promoter element (DPE), and the TFIIB recognition element (BRE). The TATA box, with the consensus sequence TATAAA, is located about 25 to 30 base pairs upstream of the TSS. It is recognized by the TATA-binding protein (TBP), a subunit of TFIID. The Inr element surrounds the TSS itself and has the consensus sequence YYANWYY (where Y is pyrimidine, W is A or T, and N is any nucleotide). The DPE is located about 28 to 32 base pairs downstream of the TSS and is recognized by TFIID in promoters that lack a TATA box. In addition to the core promoter, many eukaryotic genes have proximal promoter elements (such as GC boxes recognized by the transcription factor Sp1) and distal regulatory elements (enhancers and silencers) that modulate initiation frequency.

Step-by-Step Process of Transcription Initiation

Transcription initiation proceeds through a series of well-defined steps. Although the details differ between prokaryotes and eukaryotes, the general logic is conserved: promoter recognition, DNA unwinding, initial RNA synthesis, and promoter escape.

Promoter Binding

The first step is the binding of RNA polymerase to the promoter. In bacteria, the sigma factor scans the DNA for promoter-like sequences. The holoenzyme initially binds to the DNA in a loose, non-specific manner and slides along the duplex until it encounters a promoter. Upon encountering a promoter, the sigma factor makes specific contacts with the −35 and −10 elements, and the enzyme undergoes a conformational change that tightens its grip on the DNA. This initial binding produces the closed complex, so named because the DNA remains fully double-stranded. The closed complex is unstable and can dissociate; the equilibrium between free polymerase and promoter-bound polymerase determines the basal level of initiation.

In eukaryotes, promoter binding is more elaborate. The process begins with the binding of TFIID to the core promoter. TFIID is a large multi-protein complex that includes TBP and about 14 TBP-associated factors (TAFs). TBP recognizes the TATA box (if present) by inserting a β-sheet into the minor groove of the DNA, causing a sharp bend of about 80 degrees. In TATA-less promoters, TAFs recognize the Inr and DPE elements instead. After TFIID binds, TFIIA and TFIIB join the complex. TFIIB binds to both TBP and the DNA, and it helps recruit Pol II in association with TFIIF. The binding of Pol II–TFIIF to the TFIID–TFIIA–TFIIB complex forms the minimal PIC. TFIIE and TFIIH then join, completing the PIC. This assembly is highly ordered and requires the hydrolysis of ATP at the TFIIH step.

DNA Unwinding

The next step is the unwinding of the DNA duplex to expose the template strand. In bacteria, the transition from the closed complex to the open complex involves the melting of approximately 12 to 14 base pairs of DNA, from about −11 to +2. This unwinding is driven by the sigma factor, which interacts with the −10 element. The sigma factor recognizes the single-stranded DNA of the non-template strand and stabilizes the open state. The unwound region is called the transcription bubble. The open complex is much more stable than the closed complex, and its formation is a key regulated step. The energy for unwinding comes from the binding of the polymerase to the single-stranded DNA and from the favorable free energy change associated with the conformational rearrangement of the enzyme.

In eukaryotes, DNA unwinding requires the action of TFIIH, which possesses both ATPase and helicase activities. The XPB subunit of TFIIH uses the energy of ATP hydrolysis to melt the DNA around the TSS, forming the open complex. The unwound region in eukaryotes is typically 11 to 15 base pairs. TFIIE is required for the recruitment and regulation of TFIIH, and it also stabilizes the open complex. The open complex in eukaryotes is less stable than in bacteria, which is one reason why eukaryotic initiation requires more protein factors and ATP hydrolysis.

Abortive Initiation

Once the open complex is formed, the polymerase active site is positioned over the template strand, and the first phosphodiester bond can be formed. RNA polymerase initiates RNA synthesis by joining two NTPs that are complementary to the template strand. The first nucleotide is almost always a purine (ATP or GTP). After the first bond is formed, the polymerase adds nucleotides one at a time, extending the RNA chain.

However, the polymerase does not immediately commit to processive elongation. During the initial phase, the polymerase synthesizes short RNA products—typically 2 to 9 nucleotides in bacteria—and then releases them. This phenomenon is called abortive initiation. The polymerase remains bound to the promoter and repeatedly attempts to synthesize RNA, producing a burst of short transcripts before finally succeeding in escaping the promoter. Abortive initiation occurs because the polymerase must clear the promoter before it can enter the stable elongation mode. The transition from abortive initiation to productive elongation is called promoter escape or promoter clearance. During promoter escape, the polymerase must break its contacts with the promoter (and, in bacteria, release the sigma factor) and begin moving processively along the DNA. In bacteria, promoter escape is facilitated by the growing RNA chain, which displaces the sigma factor from its binding site. In eukaryotes, promoter escape requires the phosphorylation of the C-terminal domain (CTD) of Pol II by TFIIH, which triggers the release of many GTFs and the recruitment of elongation factors.

Transcription Initiation in Prokaryotes vs. Eukaryotes

The fundamental logic of transcription initiation is conserved across all domains of life, but the machinery and regulatory complexity differ dramatically between prokaryotes and eukaryotes. The table below summarizes the key differences.

Prokaryotic Initiation

Bacterial transcription initiation is relatively simple. The sigma factor provides promoter specificity, and the core enzyme provides catalytic activity. The entire process can be reconstituted in vitro with purified RNA polymerase, sigma factor, DNA template, and NTPs. The closed complex forms rapidly, the open complex forms within seconds to minutes depending on the promoter, and abortive initiation produces short transcripts before promoter escape. Because there is no nucleus, transcription and translation are coupled in bacteria: ribosomes can begin translating an mRNA while it is still being transcribed. This coupling is possible because initiation is fast and the mRNA is immediately accessible.

One important feature of bacterial initiation is the role of alternative sigma factors. When E. coli is subjected to heat shock, the σ32 factor replaces σ70, redirecting RNA polymerase to heat shock promoters. When flagellar genes are needed, σ28 directs transcription of those genes. This allows the bacterium to reprogram its gene expression rapidly without changing the core polymerase.

Eukaryotic Initiation

Eukaryotic transcription initiation is far more complex for several reasons. First, the DNA is packaged into chromatin, and the promoter may be occluded by nucleosomes. Before initiation can occur, chromatin must be remodeled—either by ATP-dependent chromatin remodeling complexes that slide or evict nucleosomes, or by histone-modifying enzymes that acetylate, methylate, or phosphorylate histone tails. These modifications alter the accessibility of the promoter to the transcription machinery.

Second, the PIC is much larger and more complex. The complete PIC contains Pol II, the six GTFs, and numerous additional coactivator complexes, with a total mass of several megadaltons. The assembly of this complex is highly regulated and requires ATP.

Third, eukaryotic initiation is subject to regulation by distal elements. Enhancers can be located thousands of base pairs away from the promoter, and they exert their effects through DNA looping, which brings enhancer-bound activator proteins into proximity with the PIC. This looping is facilitated by coactivator complexes such as Mediator, which bridges activators and the PIC.

Fourth, the CTD of Pol II plays a central role in coordinating transcription with RNA processing. The CTD consists of multiple repeats of the heptapeptide sequence YSPTSPS (26 repeats in yeast, 52 in humans). During initiation, the CTD is hypophosphorylated. TFIIH phosphorylates serine 5 of the CTD during promoter escape, which is important for recruiting capping enzymes that add the 5′ cap to the nascent RNA. Later, during elongation, serine 2 is phosphorylated, recruiting splicing and polyadenylation factors. The phosphorylation state of the CTD thus serves as a molecular code that links transcription initiation to downstream RNA processing events.

Regulation of Transcription Initiation

The frequency of transcription initiation is the primary determinant of gene expression levels. Cells regulate initiation through a combination of sequence-specific DNA-binding proteins, chromatin modifications, and non-coding RNAs.

Activators and Repressors

Activators are proteins that increase the rate of transcription initiation. They typically bind to specific DNA sequences near the promoter (in prokaryotes) or at enhancers (in eukaryotes) and stimulate the assembly or activity of the transcription machinery. In bacteria, the activator CAP (catabolite activator protein) binds to a site upstream of the lac promoter and recruits RNA polymerase to the promoter by making direct protein–protein contacts with the α subunit of the polymerase. This interaction stabilizes the closed complex and increases the rate of open complex formation.

Repressors decrease the rate of transcription initiation. In bacteria, the lac repressor (LacI) binds to the operator sequence, which overlaps the promoter, and physically blocks RNA polymerase from binding. Other repressors work by preventing the transition from the closed to the open complex, or by interfering with activator function.

In eukaryotes, activators and repressors often work through coactivator and corepressor complexes. Activators recruit histone acetyltransferases (HATs) such as p300/CBP, which acetylate histone tails and loosen chromatin structure, making the promoter more accessible. They also recruit the Mediator complex, which directly contacts the PIC and stimulates its assembly. Repressors recruit histone deacetylases (HDACs) and histone methyltransferases, which compact chromatin and reduce promoter accessibility.

Enhancers and Silencers

Enhancers are DNA elements that stimulate transcription from a promoter, regardless of their orientation and at distances of up to a megabase away. They are bound by multiple activator proteins, and the DNA between the enhancer and the promoter loops out so that the activators can contact the PIC. This looping is mediated by architectural proteins such as CTCF and cohesin, which organize the genome into topologically associating domains (TADs). Silencers are the repressive counterparts of enhancers; they bind repressor proteins and inhibit transcription, often by promoting chromatin compaction.

The combinatorial logic of enhancer regulation is remarkable. A single gene may have multiple enhancers, each active in a different cell type or in response to a different signal. For example, the Pax6 gene, which is essential for eye development, has multiple enhancers that drive expression in the lens, retina, and pancreas. The binding of different combinations of activators to these enhancers ensures precise spatiotemporal control of gene expression.

Epigenetic modifications also regulate initiation. DNA methylation at CpG dinucleotides in promoters is generally associated with transcriptional repression. Histone modifications such as H3K4me3 (trimethylation of lysine 4 on histone H3) are associated with active promoters, while H3K27me3 is associated with repressed promoters. These modifications are written and erased by specific enzymes and can be inherited through cell division, providing a memory of gene expression states.

How Scientists Study Transcription Initiation

Understanding transcription initiation has required the development of a wide range of experimental techniques, from biochemical reconstitution to single-molecule imaging.

In Vitro Assays

The foundational approach is the in vitro transcription assay. In this assay, purified RNA polymerase (or the PIC components) is incubated with a DNA template containing a promoter, NTPs (one of which is radiolabeled or fluorescently labeled), and buffer conditions that mimic the cellular environment—typically 10–50 mM Tris-HCl (pH 7.5–8.0), 50–150 mM KCl, 5–10 mM MgCl2, and 1 mM DTT, at 37°C for bacterial systems or 30°C for eukaryotic systems. The reaction is allowed to proceed for a defined time, then stopped, and the RNA products are separated by gel electrophoresis and detected. This assay allows researchers to measure the rate of initiation, the efficiency of promoter escape, and the effects of mutations or regulatory proteins.

A variant of this assay is the abortive initiation assay, in which only two NTPs are provided. The polymerase can synthesize a dinucleotide but cannot elongate further, so it repeatedly produces the same short product. The rate of dinucleotide synthesis reflects the rate of open complex formation and the catalytic activity of the polymerase.

ChIP and Genomics

Chromatin immunoprecipitation (ChIP) is a method for determining where a protein binds to DNA in living cells. Cells are treated with formaldehyde to cross-link proteins to DNA, the chromatin is sheared into fragments, and an antibody specific to the protein of interest is used to immunoprecipitate the protein–DNA complexes. The associated DNA is then purified and analyzed by quantitative PCR (ChIP-qPCR) or by high-throughput sequencing (ChIP-seq). ChIP-seq has been used to map the genome-wide binding sites of RNA polymerase, sigma factors, GTFs, and activators, revealing the positions of promoters and enhancers across the genome.

A related technique is PRO-seq (precision run-on and sequencing), which maps the positions of engaged RNA polymerases at nucleotide resolution. PRO-seq can distinguish between paused polymerases (which have initiated but not yet escaped the promoter) and actively elongating polymerases, providing a genome-wide view of initiation and early elongation dynamics.

Single-Molecule Studies

Single-molecule techniques have revolutionized the study of transcription initiation by allowing researchers to observe individual polymerase molecules in real time. In single-molecule FRET (smFRET), a donor fluorophore is attached to the polymerase and an acceptor fluorophore to the DNA. Changes in FRET efficiency report conformational changes in the polymerase–DNA complex as it transitions from the closed to the open complex. Optical tweezers can measure the forces and displacements associated with DNA unwinding and promoter escape. These techniques have revealed that initiation is highly stochastic: individual polymerase molecules exhibit variable dwell times at the promoter, and abortive initiation events are not deterministic but probabilistic.

Common Misconceptions and Pitfalls

Students learning about transcription initiation often encounter several conceptual difficulties. Addressing these directly can prevent persistent misunderstandings.

Misconception 1: Transcription initiation is just RNA polymerase binding to DNA. Binding is only the first step. The closed complex must isomerize to the open complex, and the polymerase must synthesize RNA and escape the promoter. A polymerase can bind a promoter and never initiate transcription. In fact, many repressors work by trapping the polymerase in a non-productive bound state.

Misconception 2: RNA polymerase binds directly to the promoter in eukaryotes. In bacteria, the sigma factor enables direct promoter recognition by the polymerase. In eukaryotes, Pol II cannot recognize promoters on its own. TFIID (via TBP) is the primary promoter recognition factor, and Pol II is recruited to the promoter through protein–protein interactions with the other GTFs. This is a fundamental difference, not a minor detail.

Misconception 3: The TATA box is present in all eukaryotic promoters. Many promoters lack a TATA box and instead rely on the Inr and DPE elements. TBP still binds, but it does so through interactions with TAFs rather than through direct sequence recognition. The TATA box is common in highly regulated, tissue-specific genes but less common in housekeeping genes.

Misconception 4: Abortive initiation is a wasteful error. Abortive initiation is not a mistake; it is a regulated step in the initiation pathway. The polymerase must undergo multiple rounds of abortive synthesis before it can escape the promoter. The number of abortive cycles is influenced by promoter sequence and regulatory factors, and it is a point of regulation.

Misconception 5: Initiation and promoter binding are synonymous with gene activation. A gene can have a promoter that is bound by RNA polymerase but still be inactive if the polymerase is paused or if elongation is blocked. In metazoans, many genes are regulated at the level of promoter-proximal pausing, where Pol II initiates and then pauses after synthesizing 20–60 nucleotides. Release from pausing, not initiation, is the regulated step for these genes.

Misconception 6: The transcription start site is always a fixed nucleotide. In many promoters, initiation occurs at multiple closely spaced start sites, a phenomenon called transcription start site heterogeneity. This is particularly common in eukaryotic promoters that lack a TATA box and Inr element. The choice of start site can affect the 5′ UTR of the mRNA and thus its translation efficiency.

Summary: Key Takeaways

• Transcription initiation is the first phase of transcription, encompassing promoter recognition, DNA unwinding, initial RNA synthesis, and promoter escape. It is the primary control point for gene expression.
• RNA polymerase is the enzyme that synthesizes RNA. In bacteria, a single core enzyme associates with sigma factors for promoter recognition. In eukaryotes, RNA polymerase II requires general transcription factors to assemble the preinitiation complex.
• Promoters are DNA sequences that direct RNA polymerase to the correct start site. Bacterial promoters contain −10 and −35 boxes; eukaryotic core promoters contain the TATA box, Inr, DPE, and BRE elements.
• Initiation proceeds through ordered steps: closed complex formation, open complex formation (DNA unwinding), abortive initiation, and promoter escape. Each step is regulated.
• Prokaryotic initiation is simple and does not require ATP. Eukaryotic initiation is complex, requires ATP for DNA unwinding and CTD phosphorylation, and is influenced by chromatin structure.
• Regulation of initiation is achieved through activators, repressors, enhancers, silencers, and epigenetic modifications. These mechanisms allow cells to respond to signals and maintain cell-type-specific gene expression.
• Transcription initiation is studied using in vitro assays, ChIP-seq, and single-molecule techniques, each of which provides complementary information about the mechanism.

Frequently Asked Questions

What is transcription initiation?

Transcription initiation is the first phase of transcription, during which RNA polymerase binds to a promoter, unwinds the DNA duplex, and synthesizes the first few nucleotides of RNA. It ends when the polymerase escapes the promoter and enters the elongation phase. Initiation is the most highly regulated step of gene expression.

What are the steps of transcription initiation?

The steps are: (1) promoter recognition and binding, forming the closed complex; (2) DNA unwinding to form the open complex; (3) synthesis of the first few RNA nucleotides, often with abortive initiation; and (4) promoter escape, in which the polymerase breaks contacts with the promoter and commits to processive elongation.

What is the difference between transcription initiation in prokaryotes and eukaryotes?

In prokaryotes, a single RNA polymerase uses sigma factors to recognize promoters directly, and initiation does not require ATP. In eukaryotes, RNA polymerase II requires six general transcription factors to assemble the preinitiation complex, ATP is required for DNA unwinding by TFIIH, and chromatin structure must be remodeled for the promoter to be accessible.

What is a promoter in transcription?

A promoter is a DNA sequence located upstream of the transcription start site that directs RNA polymerase to the correct position and orientation for transcription. Promoters contain conserved sequence elements, such as the −10 and −35 boxes in bacteria and the TATA box, Inr, and DPE in eukaryotes, which are recognized by specific proteins.

What is abortive initiation?

Abortive initiation is the repeated synthesis and release of short RNA products (2–9 nucleotides) by RNA polymerase before it successfully escapes the promoter. It is a normal and regulated part of the initiation process, not an error. The number of abortive cycles depends on the promoter sequence and regulatory factors.

How is transcription initiation regulated?

Initiation is regulated by activators and repressors that bind to DNA sequences near the promoter or at distal enhancers and silencers. These proteins influence the assembly or activity of the transcription machinery. In eukaryotes, chromatin modifications and DNA methylation also regulate promoter accessibility and initiation frequency.

Why is transcription initiation important?

Transcription initiation is the primary control point for gene expression. By regulating when and how often transcription begins, cells can respond to environmental signals, maintain cell identity, and execute developmental programs. Misregulation of initiation is a major cause of human diseases, including cancer.

Further Reading

• Basu U et al. Structure, mechanism, and regulation of mitochondrial DNA transcription initiation. The Journal of biological chemistry. 2020. PubMed 33127643
• Haberle V, Stark A. Eukaryotic core promoters and the functional basis of transcription initiation. Nature reviews. Molecular cell biology. 2018. PubMed 29946135
• Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic acids research. 1983. PubMed 6828386
• Chen X et al. Structural visualization of transcription initiation in action. Science (New York, N.Y.). 2023. PubMed 38127763
• Grapotte M et al. Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network. Nature communications. 2021. PubMed 34078885
• Alfonso-Gonzalez C et al. Sites of transcription initiation drive mRNA isoform selection. Cell. 2023. PubMed 37178687

Related Topics

• Transcription Factor
• Transcription Termination
• Transcription Translation
• Transcription Steps
• Transcription Diagram

Related Clinical & Scientific Guides

• MAPK Pathway: Mechanism, Function, and Clinical Relevance
• Mammalian Cell Culture Bioreactors: A Practical Guide
• Nucleotide Formation: Biosynthesis and Assembly of DNA/RNA Building Blocks