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Histone deacetylase 11 regulates oligodendrocyte‐specific gene expression and cell development in OL‐1 oligodendroglia cells
Author(s) -
Liu Hedi,
Hu Qichen,
D'ercole A. Joseph,
Ye Ping
Publication year - 2008
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20729
Subject(s) - biology , trichostatin a , histone deacetylase , hdac11 , histone deacetylase 5 , hdac4 , oligodendrocyte , histone h3 , histone deacetylase 2 , acetylation , histone , proteolipid protein 1 , myelin basic protein , sap30 , histone h4 , microbiology and biotechnology , histone deacetylase inhibitor , hdac10 , hdac1 , myelin , biochemistry , gene , neuroscience , central nervous system
Both in vivo and in vitro studies indicate a correlation between reduced acetylation of histone core proteins and oligodendrocyte development. The nature of these histone modifications and the mechanisms mediating them remain undefined. To address these issues, we utilized OL‐1 cells, a rat nontransformed oligodendrocyte cell line, and primary oligodendrocyte cultures. We found that the acetylated histone H3 at lysine 9 and lysine 14 (H3K9/K14ac) is reduced in both the myelin basic protein (MBP) and proteolipid protein (PLP) genes of maturing oligodendroglial OL‐1 cells, and furthermore, this temporally correlates with increases in MBP, PLP, and histone deacetylase (HDAC) 11 expression. Disruption of developmentally‐regulated histone H3 deacetylation within the MBP and PLP genes by the HDAC inhibitor trichostatin A blunts MBP and PLP expression. With its increased expression, interaction of HDAC 11 with acetylated histone H3 and recruitment of HDAC 11 to the MBP and PLP genes markedly increases in maturing OL‐1 cells. Moreover, suppressing HDAC 11 expression with small interfering RNA significantly (1) increases H3K9/K14ac globally and within the MBP and PLP genes, (2) decreases MBP and PLP mRNA expression, and (3) blunts the morphological changes associated with oligodendrocyte development. Our data strongly support a specific role for HDAC 11 in histone deacetylation and in turn the regulation of oligodendrocyte‐specific protein gene expression and oligodendrocyte development. © 2008 Wiley‐Liss, Inc.