Class I Histone Deacetylase Thd1p Promotes Global Chromatin Condensation in Tetrahymena thermophila

Abstract

Class I histone deacetylases (HDACs) regulate DNA-templated processes such as transcription. They act both at specific loci and more generally across global chromatin, contributing to acetylation patterns that may underlie large-scale chromatin dynamics. Although hypoacetylation is correlated with highly condensed chromatin, little is known about the contribution of individual HDACs to chromatin condensation mechanisms. Using the ciliated protozoan Tetrahymena thermophila, we investigated the role of a specific class I HDAC, ⌻hd1p, in the reversible condensation of global chromatin. In this system, the normal physiological response to cell starvation includes the widespread condensation of the macronuclear chromatin and general repression of gene transcription. We show that the chromatin in Thd1p-deficient cells failed to condense during starvation. The condensation failure correlated with aberrant hyperphosphorylation of histone H1 and the overexpression of CDC2, encoding the major histone H1 kinase. Changes in the rate of acetate turnover on core histones and in the distribution of acetylated lysines 9 and 23/27 on histone H3 isoforms that were found to correlate with normal chromatin condensation were absent from Thd1p mutant cells. These results point to a role for a class I HDAC in the formation of reversible higher-order chromatin structures and global genome compaction through mechanisms involving the regulation of H1 phosphorylation and core histone acetylation/ deacetylation kinetics.

Deacetylation and Methylation at Histone H3 Lysine 9 (H3K9) Coordinate Chromosome Condensation during Cell Cycle Progression

“…In fact, the Class I HDACs are involved in the development of the transcriptionally repressive state to produce high-order chromosomal structures (Ma and Schultz, 2008). At the protein levels, the expression or activity of HDACs could be increased in chromosome condensation during cell cycle progression (Li et al, 2006;Magnaghi-Jaulin and Jaulin, 2006;Parker et al, 2007;Shin et al, 2003). Moreover, as TSA treatment obviously induced H3K9 acetylation in our Western blot analysis, we assumed that the delay of G2/M phase due to co-treatment with TSA and nocodazole might have resulted in a deficiency of deacetylation of H3K9, as at least one control point.…”

A Class II Histone Deacetylase Acts on Newly Synthesized Histones in Tetrahymena

“…111-025-003). The cells were counterstained with 0.1 g/ml 4Ј,6 diamino-2-phenylindole dihydrochloride (DAPI; Sigma Chemicals) in 0.1% bovine serum albumin-phosphate-buffered saline for 10 min according to the common protocol (37).…”

Genetic analysis of common variants in the HDAC2 gene with schizophrenia susceptibility in Han Chinese

“…18,19 Among human HDACs, HDAC2 is a critical modulator of the regulation of cell proliferation, and also has an important role in gene regulation because it catalyzes a series of key reactions in physiological processes. 20 Therefore, the HDAC2 gene is a promising candidate gene for SCZ. Although there has been a previous study of the association between the HDAC2 gene and SCZ in the Han Chinese, only four single-nucleotide polymorphisms (SNPs) in a small family sample were analyzed.…”