Open AccessDeacetylase activity-independent transcriptional activation by HDAC2 during TPA-induced HL-60 cell differentiation
Author(s) -
Hyeonsoo Jung,
Jiyoung Kim,
Kee-Beom Kim,
Yun-Cheol Chae,
Yoonsoo Hahn,
Jung-Woong Kim,
Sang-Beom Seo
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0202935
Subject(s) - histone deacetylase 2 , chromatin , cellular differentiation , acetylation , histone deacetylase , transcription factor , hdac1 , biology , histone , chemistry , microbiology and biotechnology , epigenetics , chromatin immunoprecipitation , hdac3 , regulation of gene expression , gene expression , cancer research , promoter , gene , biochemistry
The human myeloid leukemia cell line HL-60 differentiate into monocytes following treatment with 12- O -tetradecanoylphorbol-13-acetate (TPA). However, the mechanism underlying the differentiation of these cells in response to TPA has not been fully elucidated. In this study, we performed ChIP-seq profiling of RNA Pol II, HDAC2, Acetyl H3 (AcH3), and H3K27me3 and analyzed differential chromatin state changes during TPA-induced differentiation of HL-60 cells. We focused on atypically active genes, which showed enhanced H3 acetylation despite increased HDAC2 recruitment. We found that HDAC2 positively regulates the expression of these genes in a histone deacetylase activity-independent manner. HDAC2 interacted with and recruited paired box 5 (PAX5) to the promoters of the target genes and regulated HL-60 cell differentiation by PAX5-mediated gene activation. Taken together, these data elucidated the specific-chromatin status during HL-60 cell differentiation following TPA exposure and suggested that HDAC2 can activate transcription of certain genes through interactions with PAX5 in a deacetylase activity-independent pathway.