Podcast
Questions and Answers
Which of the following kinases is associated with the phosphorylation of H3S10?
Which of the following kinases is associated with the phosphorylation of H3S10?
What effect does histone acetylation have on the binding of DNA to histones?
What effect does histone acetylation have on the binding of DNA to histones?
Which model explains the role of H1 phosphorylation in transcriptional regulation?
Which model explains the role of H1 phosphorylation in transcriptional regulation?
Which protein recognizes phosphorylated H3S10 at gene promoters?
Which protein recognizes phosphorylated H3S10 at gene promoters?
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What is a potential consequence of acetylation of histone N-terminal tails?
What is a potential consequence of acetylation of histone N-terminal tails?
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What is the primary role of H3-K4 methylation?
What is the primary role of H3-K4 methylation?
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How does di-methyl H3-K4 affect the methylation of H3-K9?
How does di-methyl H3-K4 affect the methylation of H3-K9?
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What is the function of the PRMT domain?
What is the function of the PRMT domain?
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What effect does the methylation of Arg 3 in histone H4 have on transcription?
What effect does the methylation of Arg 3 in histone H4 have on transcription?
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What is a characteristic effect of ubiquitylation on histones?
What is a characteristic effect of ubiquitylation on histones?
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Study Notes
Phosphorylation
- Histone phosphorylation was one of the first discovered post-translational modifications in proteins.
- H3S10 phosphorylation is particularly well studied.
- Key kinases responsible for H3S10 phosphorylation include Msk1/2 and Rsk2 (mammals), SNF1 (S. cerevisiae).
- The negative charge from phosphorylation of H1 may affect its affinity for DNA, leading to increased accessibility for the transcriptional machinery.
- Phosphorylation may also disrupt binding of other proteins to DNA.
- 14-3-3 adapter proteins (phospho-binder proteins) bind to phosphorylated H3S10, potentially regulating gene expression.
Acetylation
- Acetylation is a reversible modification occurring primarily on lysine residues, especially within the N-terminal tails of H3 and H4.
- Acetylation introduces a negative charge, reducing the strength of DNA binding to histones and opening up binding sites.
- This can decompact nucleosome arrays and open chromatin for gene activation.
- Removal of histone tails can prevent further condensation of nucleosomes beyond the 11nm fiber.
- Proteins with bromodomains bind to acetylated lysines, potentially regulating DNA-templated processes.
- Bromodomains are present in histone acetyltransferases (HATs).
- Acetylation of H3-K4, H3-K36, and H3-K79 are associated with active transcription.
- Methylation of H3-K4 plays a role in establishing euchromatic regions, preventing the spread of heterochromatin.
Lysine Methylation
- Methylation of lysine residues can be associated with both activation and repression of transcription, depending on the specific residue and the degree of methylation.
Arginine Methylation
- Methylation of specific arginine residues in histones H3 and H4 are generally associated with transcriptional activation.
- Methylation of Arg 3 in histone H4 facilitates H4 acetylation and enhances transcription activation by nuclear hormone receptors.
- Histone arginine methyltransferases (HRMTs) are a family of enzymes known as PRMTs.
PRMT Domain
- The PRMT domain is a catalytic module responsible for methylating specific arginines.
- PRMTs transfer methyl groups from SAM to arginine residues, producing mono- or dimethylarginine.
- Different PRMT domains can produce symmetric dimethylarginine or asymmetric dimethylarginine.
Ubiquitylation/Deubiquitylation and Sumoylation
- Ubiquitylation and sumoylation involve the covalent attachment of large polypeptides to histones.
- These modifications can significantly increase the size of a histone.
- Ubiquitylation can either activate or repress transcription, depending on the specific site of modification.
- No histone-specific ubiquitin-binding protein has been identified yet.
- Ubiquitylation may involve interactions with mediators, which can bind to both the ubiquitin and histone sequences.
Chromatin Opening
- Chromatin remodeling is an ATP-dependent process that opens chromatin by repositioning nucleosomes.
- The arrangement of nucleosomes at gene promoters influences the ease of access for transcription factors.
Histone Code
- The histone code is a system of signals and symbols through post-translational modifications that contribute to gene regulation.
- The histone code is consistent, combinatorial, and specific modifications are recognized by specific proteins.
- Modifications include acetylation, methylation, phosphorylation, ubiquitination, sumoylation, and others.
Histone Modifications and Evolution
- While histones are highly conserved proteins, they exhibit significant variability in post-translational modification patterns.
- Multiple modifications can occur on histone tails, contributing to the complexity of the histone code.
Mechanistic Effects of HPTM
- HPTM can directly affect chromatin structure and function through "cis effects," by influencing conformation and interactions.
- HPTM can also have "trans effects" by altering the binding of proteins to chromatin, either disrupting interactions or recruiting specific effector proteins.
- These modifications are combinatorial, meaning they can act together in patterns and sequences to regulate transcription.
- HPTM effects can be established over both short and long distances.
- Some HPTM effects are transient, while others are stable and epigenetically heritable.
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Description
Explore the mechanisms and implications of histone phosphorylation and acetylation in gene regulation. This quiz covers key kinases, the role of negative charges from these modifications, and their effects on chromatin accessibility and gene expression. Test your understanding of how these post-translational modifications contribute to cellular processes.
