16.4 Eukaryotic Transcription Gene Regulation
2 min read•june 14, 2024
Eukaryotic gene regulation is a complex dance of proteins and DNA. Transcription factors, both general and specific, play key roles in controlling when and how genes are expressed. They work together with promoter regions and other regulatory elements to fine-tune gene activity.
The process involves multiple stages, from initiation to termination. and repressors add another layer of control, allowing for precise regulation in different cell types and developmental stages. This intricate system ensures that genes are expressed at the right time and in the right amount.
Eukaryotic Transcription Gene Regulation
Transcription factors in eukaryotic regulation
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- General transcription factors (GTFs) bind to promoter regions near transcription start sites and recruit to form the (, , , , , )
- Specific transcription factors bind to or regions farther away from the promoter and interact with GTFs and other proteins to regulate transcription
- Activators increase transcription by recruiting coactivators (, ) and complexes ()
- Repressors decrease transcription by blocking access to promoter regions or recruiting corepressors (, )
Structure of eukaryotic promoter regions
- located near the transcription start site contains binding sites for GTFs and RNA polymerase II (, , )
- located upstream of the core promoter contains binding sites for specific transcription factors and regulates basal transcription levels
- (enhancers and silencers) located farther away from the transcription start site can be upstream, downstream, or within introns and contains binding sites for specific transcription factors that regulate transcription in a cell-type or developmental stage-specific manner
- , such as enhancers and silencers, play a crucial role in modulating gene expression by interacting with
Enhancers and repressors in transcription control
- Enhancers are binding sites for activator proteins that increase transcription by looping DNA to interact with promoter regions and recruit coactivators and chromatin remodeling complexes
- Repressors are binding sites for repressor proteins that decrease transcription by blocking access to promoter regions or recruiting corepressors
- Enhancer-promoter interactions involve looping of DNA to bring enhancers and promoters into close proximity, facilitated by proteins like and , allowing for precise control of gene expression in specific cell types and developmental stages
Stages of transcription and regulation
- : The assembly of the preinitiation complex and recruitment of RNA polymerase II to the promoter
- : The process of RNA synthesis as the polymerase moves along the DNA template
- : The release of the newly synthesized RNA and dissociation of the polymerase from the DNA template
- Each stage is subject to regulation by various factors and mechanisms, including that can affect chromatin structure and accessibility
Key Terms to Review (32)
Chromatin remodeling: Chromatin remodeling refers to the dynamic process of restructuring chromatin to regulate access to DNA, enabling or restricting the transcription of genes. This process involves the repositioning of nucleosomes, making DNA either more accessible for transcription or compacted to prevent gene expression. Chromatin remodeling is crucial for various cellular processes, including DNA replication, gene regulation, and maintaining genome stability.
Cis-acting element: A cis-acting element is a region of non-coding DNA that regulates the transcription of nearby genes. These elements are typically located on the same DNA molecule as the gene they control and include promoters, enhancers, and silencers.
Cis-regulatory elements: Cis-regulatory elements are regions of non-coding DNA that regulate the transcription of nearby genes. These elements play a critical role in gene expression by providing binding sites for transcription factors and other regulatory proteins, influencing how, when, and where a gene is expressed. They are essential for controlling the timing and level of gene expression in response to various signals and environmental changes.
Cohesin: Cohesin is a protein complex that plays a crucial role in the regulation of chromosome structure and function, especially during cell division. It is responsible for holding sister chromatids together after DNA replication, ensuring accurate segregation into daughter cells during mitosis and meiosis. Beyond its structural role, cohesin also influences gene expression by interacting with regulatory regions of DNA, linking chromatin architecture to transcriptional control.
Core promoter: The core promoter is a region of DNA located immediately upstream of the transcription start site, essential for the initiation of transcription in eukaryotic cells. It contains specific sequences that are recognized by transcription factors and RNA polymerase, serving as the foundational platform for gene regulation. Its interaction with various regulatory elements determines the precise control of gene expression.
CTCF: CTCF (CCCTC-binding factor) is a highly conserved zinc-finger protein that plays a critical role in the regulation of gene expression in eukaryotic cells. It functions as an architectural protein that organizes chromatin structure, influencing transcriptional regulation by establishing boundaries between active and inactive regions of the genome. CTCF's ability to mediate long-range interactions within the genome contributes significantly to enhancer-promoter interactions and the overall three-dimensional arrangement of DNA.
Distal Promoter: A distal promoter is a regulatory DNA sequence located far from the transcription start site of a gene, playing a crucial role in the initiation of transcription in eukaryotic cells. These regions often contain binding sites for transcription factors that enhance or repress gene expression, making them essential for precise gene regulation. Distal promoters can interact with the core promoter through looping mechanisms, allowing for complex control of transcription in response to various cellular signals.
Downstream promoter element: A downstream promoter element is a regulatory DNA sequence located downstream of the transcription start site that enhances the efficiency of gene transcription in eukaryotic cells. These elements are critical for the binding of transcription factors and RNA polymerase, ultimately influencing gene expression levels. They work in conjunction with other promoter elements to ensure proper regulation of transcription.
Enhancer: An enhancer is a regulatory DNA sequence that can significantly increase the transcription of specific genes. These elements work by binding to transcription factors, which then interact with the core promoter and other proteins to facilitate the assembly of the transcription machinery. Enhancers play a critical role in gene expression regulation by controlling when and where specific genes are activated in eukaryotic cells.
Enhancers: Enhancers are short regions of DNA that can significantly increase the transcription of genes. They function by binding to specific transcription factors and looping to interact with promoters, even if located far away.
Epigenetic modifications: Epigenetic modifications are chemical changes to DNA or histone proteins that regulate gene expression without altering the underlying DNA sequence. These modifications play a critical role in the regulation of transcription in eukaryotic cells, affecting how genes are turned on or off in response to various signals and environmental factors.
Histone acetyltransferases: Histone acetyltransferases (HATs) are enzymes that add acetyl groups to the lysine residues on histone proteins, leading to a more relaxed chromatin structure and enhanced gene expression. By modifying histones, HATs play a crucial role in regulating the accessibility of DNA for transcription and are essential for various cellular processes, including differentiation and response to environmental signals.
Histone deacetylases: Histone deacetylases (HDACs) are enzymes that remove acetyl groups from the lysine residues on histone proteins, leading to a more compact chromatin structure and generally resulting in the repression of gene expression. By regulating the acetylation status of histones, these enzymes play a crucial role in controlling access to DNA for transcription factors and other regulatory proteins, impacting both epigenetic modifications and transcriptional regulation.
Initiator element: The initiator element is a specific DNA sequence located at the promoter region of a gene, playing a critical role in the initiation of transcription in eukaryotic cells. This element serves as a recognition site for transcription factors and RNA polymerase II, which together help to form the transcription initiation complex necessary for gene expression. Its presence and proper functioning are essential for the regulation of gene transcription in response to various cellular signals.
Mediator complex: The Mediator complex is a multi-protein complex that serves as a crucial bridge between gene-specific transcription factors and the RNA polymerase II machinery, facilitating the transcription of DNA into RNA in eukaryotic cells. It plays a key role in the regulation of gene expression by integrating signals from various transcription factors, thus influencing the recruitment and activity of RNA polymerase II at specific promoters.
Polycomb group proteins: Polycomb group proteins are a family of proteins that play crucial roles in gene regulation, particularly in the maintenance of transcriptional repression during development. They are involved in modifying chromatin structure, allowing for stable silencing of genes, which is essential for controlling cellular differentiation and identity. These proteins form multiprotein complexes that can modify histones and influence DNA accessibility, ultimately impacting gene expression.
Preinitiation complex: The preinitiation complex is a crucial assembly of proteins that forms on the promoter region of a gene, preparing it for transcription in eukaryotic cells. This complex includes RNA polymerase II, general transcription factors, and other regulatory proteins that work together to position the polymerase correctly and initiate the transcription process. It plays an essential role in the precise regulation of gene expression, ensuring that genes are transcribed at the right time and in the right amounts.
Proximal promoter: The proximal promoter is a region of DNA located just upstream of a gene that plays a critical role in the initiation of transcription by providing binding sites for transcription factors and RNA polymerase. This region is essential for regulating gene expression, as it interacts with both general and specific transcription factors that influence the efficiency and rate of transcription. The proximal promoter is part of the larger promoter region, which includes the core promoter and additional regulatory elements.
RNA polymerase II: RNA polymerase II is a crucial enzyme in eukaryotic cells responsible for synthesizing messenger RNA (mRNA) from DNA during the transcription process. It plays a key role in gene expression by converting genetic information encoded in DNA into RNA, which can then be translated into proteins. This enzyme also facilitates the processing of pre-mRNA, including capping and polyadenylation, which are vital for mRNA stability and translation efficiency.
Silencer: A silencer is a DNA sequence that can bind transcription factors to inhibit the transcription of a gene. These regulatory elements play a crucial role in the precise control of gene expression, allowing cells to respond to various signals by turning genes off when they are not needed, thus ensuring proper development and functioning.
SWI/SNF complex: The SWI/SNF complex is a multi-subunit protein complex that plays a crucial role in the regulation of gene expression by remodeling chromatin structure. It utilizes ATP to alter the positioning of nucleosomes, thereby facilitating access for transcription factors and other regulatory proteins to DNA. This chromatin remodeling is essential for proper gene activation and repression, making the SWI/SNF complex vital in controlling cellular processes such as differentiation and response to environmental signals.
TATA box: The TATA box is a DNA sequence found in the promoter region of many genes in eukaryotes, essential for the initiation of transcription. It serves as a binding site for transcription factors and RNA polymerase II, playing a critical role in the regulation of gene expression by facilitating the formation of the transcription initiation complex.
TFIIA: TFIIA is a transcription factor that plays a vital role in the initiation of eukaryotic transcription by enhancing the binding of RNA polymerase II to the promoter region of genes. It acts as a coactivator that helps stabilize the interaction between the transcriptional machinery and DNA, facilitating the formation of a pre-initiation complex necessary for gene expression.
TFIIB: TFIIB is a general transcription factor essential for the initiation of transcription in eukaryotic cells. It plays a crucial role by interacting with RNA polymerase II and helping to recruit additional factors necessary for the formation of the transcription pre-initiation complex, which is vital for gene expression.
TFIID: TFIID is a crucial multi-subunit protein complex that plays a key role in initiating transcription by RNA polymerase II in eukaryotic cells. This complex is made up of the TATA-binding protein (TBP) and several TBP-associated factors (TAFs), which together recognize and bind to the promoter region of a gene, allowing the assembly of the transcription machinery and regulating gene expression.
TFIIE: TFIIE is a crucial transcription factor involved in the initiation of transcription by RNA polymerase II in eukaryotic cells. It plays a key role in the assembly of the transcription pre-initiation complex and is essential for the recruitment of RNA polymerase II to the promoter region of genes, influencing the overall transcription process and gene expression regulation.
TFIIF: TFIIF, or Transcription Factor II F, is a multi-subunit protein complex that plays a crucial role in eukaryotic transcription by interacting with RNA polymerase II and facilitating the formation of the pre-initiation complex at promoter regions. It is essential for the recruitment of RNA polymerase II to specific gene promoters and is involved in the regulation of transcriptional activation, making it vital for proper gene expression.
TFIIH: TFIIH is a multi-subunit protein complex that plays a critical role in the process of transcription in eukaryotic cells. It is essential for the unwinding of DNA at the transcription start site and has functions in nucleotide excision repair, linking these two vital cellular processes. The complex is composed of both ATP-dependent helicase activity, which helps in separating the DNA strands, and kinase activity, which phosphorylates the C-terminal domain of RNA polymerase II, crucial for the transition from transcription initiation to elongation.
Trans-acting factors: Trans-acting factors are regulatory proteins that control gene expression by binding to specific DNA sequences, influencing the transcription of genes located on different chromosomes or regions. These factors can act from a distance, meaning they can regulate genes that are not physically adjacent, thereby playing a crucial role in the complexity of gene regulation in eukaryotic cells. They include transcription factors, repressors, and activators that interact with the transcription machinery to enhance or inhibit gene expression.
Transcription elongation: Transcription elongation is the process during gene expression where RNA polymerase synthesizes a strand of RNA from a DNA template, extending the RNA molecule by adding ribonucleotides one by one. This phase occurs after the initiation of transcription and is crucial for creating a complete RNA transcript that carries the genetic information required for protein synthesis. During this phase, RNA polymerase moves along the DNA, unwinding the double helix and synthesizing RNA in the 5' to 3' direction.
Transcription initiation: Transcription initiation is the process by which RNA polymerase binds to a specific region of DNA at the promoter site to start synthesizing RNA from a DNA template. This step is crucial in gene regulation, as it determines whether a gene will be expressed or not, and involves several key components such as transcription factors and enhancers that help facilitate the assembly of the transcription machinery.
Transcription termination: Transcription termination is the process by which RNA synthesis is concluded, signaling the end of transcription in eukaryotic cells. This crucial step ensures that RNA polymerase disengages from the DNA template and releases the newly synthesized RNA molecule. The mechanisms that govern transcription termination in eukaryotes involve various factors and sequences that help regulate gene expression, linking this process to broader gene regulation mechanisms.