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Rapid activation of the bivalent gene Sox21 requires displacement of multiple layers of gene‐silencing machinery
Author(s) -
Chakravarthy Harini,
Ormsbee Briana D.,
Mallanna Sunil K,
Rizzino Angie
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-166926
Subject(s) - prc2 , microbiology and biotechnology , biology , gene silencing , bivalent (engine) , histone , chromatin , regulation of gene expression , gene , chromatin immunoprecipitation , sox2 , bivalent chromatin , embryonic stem cell , genetics , histone h3 , gene expression , chromatin remodeling , chemistry , promoter , organic chemistry , metal
The rapid formation of numerous tissues during development is highly dependent on the swift activation of key developmental regulators. Recent studies indicate that many key regulatory genes are repressed in embryonic stem cells (ESCs), yet poised for rapid activation due to the presence of both activating (H3K4 trimethylation) and repressive (H3K27 trimethylation) histone modifications (bivalent genes). However, little is known about bivalent gene regulation. In this study, we investigated the regulation of the bivalent gene Sox21, which is activated rapidly when ESCs differentiate in response to increases in Sox2. Chromatin immunoprecipitation demonstrated that prior to differentiation, the Sox21 gene is bound by a complex array of repressive and activating transcriptional machinery. Upon activation, all identified repressive machinery and histone modifications associated with the gene are lost, but the activating modifications and tran‐scriptional machinery are retained. Notably, these changes do not occur when ESCs differentiate in response to retinoic acid. Moreover, ESCs lacking a functional PRC2 complex fail to activate this gene, apparently due to its association with other repressive complexes. Together, these findings suggest that bivalent genes, such as Sox21, are silenced by a complex set of redundant repressive machinery, which exit rapidly in response to appropriate differentiation signals.—Chakravarthy, H., Ormsbee, B. D., Mallanna, S. K., Rizzino, A. Rapid activation of the bivalent gene Sox21 requires displacement of multiple layers of gene‐silencing machinery. FASEB J. 25, 206–218 (2011). www.fasebj.org