To form chromatin, DNA is tightly wrapped around nuclear proteins called histones. The repeating DNA-histone complex, which consists of 146 base pairs of double-stranded DNA wrapped around eight core histone proteins (H2A, H2B, H3 and H4), is called a nucleosome. Histone proteins are involved in structural organization of chromatin in eukaryotic cells. They can undergo various posttranslational modifications (PTMs) such as methylation/demethylation and acetylation/deacetylation, which can alter their interaction with DNA and nuclear proteins resulting in remodeling of chromatin structure and transcriptional activation or repression. The H3 and H4 histones for example, have long tails protruding from the nucleosome which can be covalently modified at several sites of the N-terminal domain. In addition, histone modifications can also recruit ATP-dependent remodeling enzymes to reposition nucleosomes.
Histone acetylation occurs by the enzymatic addition of an acetyl group (COCH3) from acetyl coenzyme A by histone acetyltransferases (HATs). The process of histone acetylation is tightly involved in the regulation of many cellular processes including chromatin dynamics and transcription, gene silencing, cell cycle progression, apoptosis, differentiation, DNA replication, DNA repair, nuclear import, and neuronal repression. Histone deacetylaces (HDACs) catalyze the hydrolytic removal of acetyl groups from histone lysine residues. Both HATs and HDACs play critical roles in various cellular processes involving histones H3 and H4. Rpd3S is a histone deacetylase complex that is recruited by elongating RNA Pol II at coding regions to remove histone acetylation. This activity is dependent on H3K36 methylation. To investigate how chromatin remodelers regulate the histone deacetylase complex Rpd3S, researchers in the department of molecular biology at UT Southwestern Medical Center in Dallas, Texas created a series of nucleosome templates with varying linker DNA lengths and used techniques including EMSA, HAT and HDAC assays to evaluate enzyme activity.
Their findings are summarized below:
Learn all about it and read more about their findings here: Lee C et al., Chromatin Remodelers Fine-Tune H3K36me-Directed Deacetylation of Neighbor Nucleosomes by Rpd3S, Molecular Cell (2013).
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