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Histone deacetylase activity is required for embryonic stem cell differentiation
Author(s) -
Lee JeongHeon,
Hart Suzanne R.L.,
Skalnik David G.
Publication year - 2004
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.10250
Subject(s) - biology , trichostatin a , euchromatin , cellular differentiation , chromatin , heterochromatin , microbiology and biotechnology , hdac11 , epigenetics , chromatin remodeling , histone , ezh2 , embryonic stem cell , histone deacetylase , histone methyltransferase , genetics , gene
Mammalian development requires commitment of cells to restricted lineages, which requires epigenetic regulation of chromatin structure. Epigenetic modifications were examined during in vitro differentiation of murine embryonic stem (ES) cells. Global histone acetylation, a euchromatin marker, declines dramatically within 1 day of differentiation induction and partially rebounds by day 2. Histone H3‐Lys9 methylation, a heterochromatin marker, increases during in vitro differentiation. Conversely, the euchromatin marker H3‐Lys4 methylation transiently decreases, then increases to undifferentiated levels by day 4, and decreases by day 6. Global cytosine methylation, another heterochromatin marker, increases slightly during ES cell differentiation. Chromatin structure of the Oct4 and Brachyury gene promoters is modulated in concert with their pattern of expression during ES cell differentiation. Importantly, prevention of global histone deacetylation by treatment with trichostatin A prevents ES cell differentiation. Hence, ES cells undergo functionally important global and gene‐specific remodeling of chromatin structure during in vitro differentiation. genesis 38:32–38, 2004. © 2003 Wiley‐Liss, Inc.