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What is transcriptional regulation and why is it important?
Transcriptional regulation controls the amount and timing of gene product production, enabling processes like cell differentiation and response to environmental changes.
What roles do activators and repressors play in transcription?
Activators increase transcription levels, while repressors decrease transcription levels for certain genes.
Where do regulatory proteins typically bind in prokaryotic and eukaryotic genes?
In prokaryotes, regulatory proteins bind near or overlapping the promoter (called operators). In eukaryotes, they bind to distal regulatory sequences called enhancers, often thousands of base pairs away.
What is the function of locus control regions (LCRs) in higher eukaryotes?
LCRs contain enhancer and insulator elements and regulate gene expression through recruitment of transcriptional machinery via DNA looping.
What are the functional domains of regulatory proteins?
Regulatory proteins have a DNA-binding domain and may include domains for oligomerization, transcriptional activation/repression, or interaction with other regulators.
What are co-activators and co-repressors, and how do they function?
They do not bind DNA directly but are recruited by DNA-binding regulatory proteins. They help control transcription by interacting with transcription machinery or modifying chromatin.
How can regulatory protein activity be modulated?
Through allosteric effectors, covalent modifications (e.g. phosphorylation), or changes in subcellular localization.
What is the role of chromatin structure in transcription regulation?
Chromatin remodeling and histone modifications influence transcription. Hyperacetylation promotes transcription, while hypoacetylation represses it.
Name two key effects of post-translational histone modifications on transcription.
(1) Alter histone charge to influence DNA interaction. (2) Create binding sites for regulatory proteins.
What is the histone code hypothesis?
It suggests that specific combinations of histone modifications lead to distinct transcriptional outcomes.
Describe the helix-turn-helix DNA-binding motif.
Composed of two alpha helices linked by a turn; the C-terminal helix fits in the major groove. Often functions as a dimer with symmetrical DNA recognition.
What is a homeodomain and its function?
A monomeric helix-turn-helix found in eukaryotes; helix 3 fits in the major groove, while the N-terminal arm contacts the minor groove. Plays a role in development.
Describe the structure and function of zinc finger motifs.
Zinc fingers have alpha helices and beta strands stabilized by a zinc ion. Each finger recognizes 2-3 DNA bases. Common in human genome.
What is the bZIP DNA-binding motif?
It consists of two long alpha helices with leucine zippers that form a dimer. The N-terminal end binds DNA in the major groove.
Compare bZIP and bHLH DNA-binding proteins.
Both form dimers. bZIP has a single long helix per monomer; bHLH has two helices per monomer connected by a loop, forming a four-helix bundle.
How do beta sheets and loops contribute to DNA recognition?
They can mediate DNA major groove recognition, as seen in proteins like MetJ, NF-κB, and immunoglobulins.
How does the Trp operon function in E. coli?
When tryptophan is abundant, it binds to the Trp repressor, enabling it to bind DNA and block transcription. When tryptophan is scarce, the repressor does not bind DNA, and the operon is expressed.
How does the Catabolite Activator Protein (CAP) enhance transcription in E. coli?
When glucose is low, cAMP binds CAP, increasing its DNA affinity. CAP then enhances RNA polymerase binding by contacting its α subunits.
Explain how the lac operon integrates signals from glucose and lactose levels.
CAP responds to glucose
What happens to lac operon expression when both glucose and lactose are high?
Transcription is weak because CAP is inactive (no cAMP), though LacI is inactivated by allolactose.
What happens to the lac operon when glucose is high and lactose is low?
Transcription is off. CAP is inactive due to low cAMP, and LacI binds the operator, blocking transcription.
What determines cell identity in eukaryotes?
Transcription regulation, which drives different proteomes from the same genome, leading to cell differentiation and specialization.
How do allosteric effectors regulate transcription?
They bind to regulatory proteins and alter their conformation, changing their DNA-binding ability or interactions with other proteins.
What are two examples of allosteric effectors?
cAMP (a nucleotide) and estrogen (a hormone).
What is the difference between promoter strength and targeted gene regulation?
Promoter strength is a basic, inherent feature of a gene, while targeted regulation involves activators, repressors, and other complex mechanisms acting on initiation, elongation, or the RNA itself.
What types of chromatin-modifying proteins are involved in transcription regulation?
ATP-dependent chromatin remodeling complexes, histone modification enzymes, and histone chaperones.
What is the role of histone acetyltransferases (HATs) and histone deacetylases (HDACs)?
HATs activate transcription by acetylating histones; HDACs repress transcription by removing acetyl groups.
What is the role of architectural DNA-binding proteins in transcription regulation?
They assist in DNA looping so distal regulatory sequences can interact with RNA polymerase and other machinery.