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Questions and Answers
What role do the +Arg side chains of histones H3 and H4 play in DNA interaction?
What role do the +Arg side chains of histones H3 and H4 play in DNA interaction?
How can the nucleosome core particle (NCP) be characterized?
How can the nucleosome core particle (NCP) be characterized?
What is the function of the H1 histone in relation to chromatin structure?
What is the function of the H1 histone in relation to chromatin structure?
Which of the following describes the structural models of chromatin?
Which of the following describes the structural models of chromatin?
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What happens to the chromatin volume during mitosis?
What happens to the chromatin volume during mitosis?
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What is the function of transcription factors in gene regulation?
What is the function of transcription factors in gene regulation?
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What characterizes super-enhancers?
What characterizes super-enhancers?
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Which statement about nucleosomes is incorrect?
Which statement about nucleosomes is incorrect?
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What is the relationship between transcription factors and nucleosomes?
What is the relationship between transcription factors and nucleosomes?
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What defines a pioneer transcription factor?
What defines a pioneer transcription factor?
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What does cohesion ring looping facilitate in transcription regulation?
What does cohesion ring looping facilitate in transcription regulation?
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Which technique is implied to study TF invasion regarding nucleosomes?
Which technique is implied to study TF invasion regarding nucleosomes?
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What role do coregulators play in the transcription initiation complex?
What role do coregulators play in the transcription initiation complex?
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Study Notes
Transcription Regulation (Eukaryotic)
- Physical interactions occur between promoters (near genes) and enhancers (far from genes).
- Cis regulatory interactions are encouraged by cohesion ring looping.
- Enhancers and promoters are linked by sequence-specific transcription factors (TFs), co-regulators, mediator complex, and polymerase. The process culminates in a complex involving ~56 polypeptides, general TFs, TFIID TAFs, and mediator.
- The Polymerase CTD may interact with the mediator complex.
Transcription Factors (TFs)
- Sequence-specific TFs regulate specific genes based on their sequence.
- Different binding domains include Zinc-Finger (e.g., CTCF), Leucine zipper, Helix-turn-helix.
- Master developmental regulators and reprogramming factors (e.g., fibroblast to muscle/neuron) are TFs.
- TFs bind nucleosomes, but often destabilize DNA structure.
- Pioneer TFs bind with high affinity, increasing nucleosome accessibility for other TFs.
Enhancers
- Enhancers typically range from 1 kb to 1 Mb away from target genes.
- Located upstream or downstream of genes.
- Orientation of enhancers is independent.
- Super-enhancers are clusters of enhancers that regulate pluripotency genes/oncogenes.
- Epigenetic signatures (e.g., H3K27ac) and lack of nucleosomes can identify enhancers.
Nucleosomes
- Nucleosomes are the fundamental units of chromatin. DNA wraps around histone octamers (2 each of H2A, H2B, H3, and H4).
- Organization proceeds from 10nm beads-on-a-string, to 30nm fibers (zigzag or solenoid), to 300-700 nm chromatids and ultimately to 1400 nm chromosomes.
- Nucleosomes are absent at active promoters and enhancers, which are therefore nucleosome-depleted regions (NDRs).
- Histone octamers are comprised of two H2A-H2B dimers and two H3-H4 dimers.
- DNA wraps around the histone core in a left-handed manner, forming nucleosome core particles (NCPs). Histone tails are unstructured and are often modified.
Chromatin Remodeling
- Chromatin remodeling can involve spontaneous unwrapping/sliding.
- Or be ATP-driven, using factors from families like SNF2, CHD1, ISWI, and INO80 (distinct activities termed pushers (SWI/SNF), pullers (ISW2), and spacers (ISW1)).
- Histone modification (acetylation, methylation) is a mechanism of transcription regulation.
Chromatin Structure
- Two models for chromatin configuration exist: a zigzag model and a two-start helix model.
- Various post-translational modifications (PTMs) on histone tails can influence DNA binding and consequently the chromatin state.
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Description
Explore the complex mechanisms of transcription regulation in eukaryotic cells. This quiz covers the interactions between promoters and enhancers, the role of transcription factors, and the composition of regulatory complexes. Test your knowledge on the various elements that contribute to gene expression.