A chromatin activity-based chemoproteomic approach reveals a transcriptional repressome for gene-specific silencing.
A chromatin activity-based chemoproteomic approach reveals a transcriptional repressome for gene-specific silencing.
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DOI：
10.1038/ncomms6733
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发表时间：
2014-12-15
影响因子：
16.6
通讯作者：
Chen, Xian
中科院分区：
文献类型：
--
作者：
Liu, Cui;Yu, Yanbao;Liu, Feng;Wei, Xin;Wrobel, John A.;Gunawardena, Harsha P.;Zhou, Li;Jin, Jian;Chen, Xian
Immune cells develop endotoxin tolerance (ET) after prolonged stimulation. ET increases the level of a repression mark H3K9me2 in the transcriptional-silent chromatin specifically associated with pro-inflammatory genes. However, it is not clear what proteins are functionally involved in this process. Here we show that a novel chromatin activity based chemoproteomic (ChaC) approach can dissect the functional chromatin protein complexes that regulate ET-associated inflammation. Using UNC0638 that binds the enzymatically active H3K9-specific methyltransferase G9a/GLP, ChaC reveals that G9a is constitutively active at a G9a-dependent mega-dalton repressome in primary endotoxin-tolerant macrophages. G9a/GLP broadly impacts the ET-specific reprogramming of the histone code landscape, chromatin remodeling, and the activities of select transcription factors. We discover that the G9a-dependent epigenetic environment promotes the transcriptional repression activity of c-Myc for gene-specific co-regulation of chronic inflammation. ChaC may be also applicable to dissect other functional protein complexes in the context of phenotypic chromatin architectures.
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DOI：
10.1084/jem.20112343
发表时间：
2012-04-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fang TC;Schaefer U;Mecklenbrauker I;Stienen A;Dewell S;Chen MS;Rioja I;Parravicini V;Prinjha RK;Chandwani R;MacDonald MR;Lee K;Rice CM;Tarakhovsky A
通讯作者：
Tarakhovsky A
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
64.8
作者：
Foster, Simmie L.;Hargreaves, Diana C.;Medzhitov, Ruslan
通讯作者：
Medzhitov, Ruslan
DOI：
10.1038/nrm3545
发表时间：
2013-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.4
作者：
Chen, X;Smith, LM;Bradbury, EM
通讯作者：
Bradbury, EM