Week 6 Flashcards
(10 cards)
How does H3K27me3 influence gene expression, and which protein complex is primarily responsible for its catalyzation?
H3K27me3 is a repressive histone modification that leads to transcriptional silencing. It is catalyzed by the Polycomb Repressive Complex 2 (PRC 2) specifically by EZH2 methyltransferase.
What is histone code, how does it affect gene regulation?
The histone code proposes that specific combinations of histone post-translational modifications (PTMs) act as a code to recruit effector proteins that interpret these marks to influence chromatin structure and gene expression. This adds regulatory layer beyond the genetic code.
Facultative vs constitutive heterochromatin
Constitutive heterochromatin (centromeres) is permanently silenced and enriched with H3K9 me3. Facultative heterochromatin (e.g. inactve X chromosome) is developmentally regulated and associated with H3K27me3.
Bromodomains and chromodomains in histone modification recognition.
Bromodomains recognize acetylated lysines (H3K9me3, often associated with repression.Chromodomains recognize methylated lysines.
Explain how histone acetylation affects chromatin accessibility and name one enzyme responsible for this modification.
Histone acetylation neutralizes the posiive charge of lysine residues, weakening histone-DNA interactions and making chromatin more accessible to transcription machinery. Histone acetyltransferases (HATs) such as p300 are responsible.
How does the TET enzyme family contribute to active DNA demethylation, and how is this connected to histone modification?
TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcystosine and further derivatives, leading to DNA demethylation. This process is often coordinated with histone modifications such as H3K4me3 at active promoter sites.
Which histone variant is typically associated with DNA damage repair, and how does its depression affect chromatin structure?
H2A.X is phosphorylated to y-H2A.X upon DNA damage, marking the region for recruitment of repair proteins. This modification promotes chromatin relaxation and access to damaged DNA.
What is the role of histone ubiquitination in transcriptional regulation, and which residues are commonly modified?
Histone ubiquitination can either activate or repress transcription depending on context. H2B ubiquitination at K120 is associated with active transcription and facilitates subsequent H3K4 and H3K7 methylation.
Discuss the mechanism by which the nucleosome remodeling complex SWI/SNF contributes to gene expression changes.
SWI/SNF uses ATP to reposition, eject, or restructure nucleosomes, increasing accessibility of DNA to transcription factors and the transcriptional machinery. It’s often recruited by transcriptional activators.
How does crosstalk between histone modifications regulate chromatin states?
Crosstalk (interplay between different PTMs that influence each other. For instance, H2B ubiquitination is required for H3K4 and H3K79 methylation - thus linking transcription initiation with elongation.
