Chromatin structure and remodeling a) Which histone domain or region is subject

Question

Chromatin structure and remodeling a) Which histone domain or region is subject to more intensive posttranslational modifications? b) Histone H3 has been acetylated. Explain how this could change the interaction of the histone with the DNA and the interaction of a transcription factor with nearby DNA-binding sites. c) How can ATP-dependent chromatin remodeling complexes change the interaction of a transcription factor with its DNA binding site. d) Which histones are poised to maintain the epigenetic memory through cell division and why.

Explanation / Answer

Answer:

4. a. Histone domains of Canonical H2A and variant macroH2A1 are subjected to more intensive posttranslational modifications.

b. Lysine is positively charged and adding an acetyl group to the lysine in histones reduces the interaction between histones and chromatin. The DNA can open up, allowing transcription machinery to launch on the DNA template and facilitate transcription.

Acetylation of H3 histones activates gene transcription by attracting other transcription machinery involving transcription factors. The acetylation site provides a point of protein recognition where transcription factors interact with the bromodomains of acetylated histone tails.

c. Nucleosomes play a major role in all aspects of eukaryotic transcriptional regulation by limiting access to sites on the DNA, e.g., transcription factor binding sites. Nucleosomes play a regulatory role, because they can be altered in two principal ways:

(i) through covalent modifications

(ii) through nucleosome structure alterations: They may change position with respect to the DNA sequence, the path of the DNA around nucleosomes may be altered, and histones may be removed.

A study of the nucleosome dependent ATPase, ISWI in yeast illustrates the involvement of ATP-dependent chromatin remodeling in transcriptional repression by setting up inaccessible chromatin structures at promoters.

All known classes of chromatin remodeling ATPases are recruited to specific sites such as promoters by direct interaction with sequence specific DNA binding transcription factors. In all cases the movement of nucleosomes may either increase or reduce the accessibility of a site for DNA binding proteins such as transcription factors. Therefore, the nucleosome remodeling reaction may lead to transcriptional activation or repression and the same remodeling factor may operate in both ways.

d. The Trithorax complex involved in Drosophila embryo development mediates methylation of histone H3 on lysine 4 (H3K4me) and is required to maintain genes in an active state.

The PcG proteins have two biochemically characterized repressive complexes: PRC1 and PRC2. PRC2 methylates histone 3 lysine 27 (H3K27me) at genes targeted for silencing. PRC1 binds H3K27me and induces spreading of structural changes in the chromatin.

This histone mark has been proposed to act as a repressive “bookmark” during mitosis where it is maintained through cell division and transmitted through DNA replication in the absence of the initial stimuli

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