Remodeling of the Enhancer Landscape during Macrophage Activation Is Coupled to Enhancer Transcription

被引：500

作者：

Kaikkonen, Minna U. ^{[1
,3
]}

Spann, Nathanael J. ^{[1
]}

Heinz, Sven ^{[1
]}

Romanoski, Casey E. ^{[1
]}

Allison, Karmel A. ^{[1
]}

Stender, Joshua D. ^{[1
]}

Chun, Hyun B. ^{[1
]}

Tough, David F. ^{[4
]}

Prinjha, Rab K. ^{[4
]}

Benner, Christopher ^{[5
]}

Glass, Christopher K. ^{[1
,2
]}

机构：

[1] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[3] Univ Eastern Finland, Dept Biotechnol & Mol Med, AI Virtanen Inst, Kuopio 70211, Finland

[4] GlaxoSmithKline R&D, Med Res Ctr, Epinova DPU, Immunoinflammat Therapy Area, Stevenage SG1 2NY, Herts, England

[5] Salk Inst Biol Studies, La Jolla, CA 92037 USA

来源：

MOLECULAR CELL | 2013年 / 51卷 / 03期

基金：

芬兰科学院;

关键词：

GENOME-WIDE ANALYSIS; GENE-EXPRESSION; CHROMATIN ACCESSIBILITY; HISTONE H3; IN-VIVO; P-TEFB; ELONGATION; DISTINCT; METHYLATION; RECRUITMENT;

D O I：

10.1016/j.molcel.2013.07.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent studies suggest a hierarchical model in which lineage-determining factors act in a collaborative manner to select and prime cell-specific enhancers, thereby enabling signal-dependent transcription factors to bind and function in a cell-type-specific manner. Consistent with this model, TLR4 signaling primarily regulates macrophage gene expression through a pre-existing enhancer landscape. However, TLR4 signaling also induces priming of 3,000 enhancer-like regions de novo, enabling visualization of intermediates in enhancer selection and activation. Unexpectedly, we find that enhancer transcription precedes local mono- and dimethylation of histone H3 lysine 4 (H3K4me1/2). H3K4 methylation at de novo enhancers is primarily dependent on the histone methyltransferases MII1, MII2/4, and MII3 and is significantly reduced by inhibition of RNA polymerase II elongation. Collectively, these findings suggest an essential role of enhancer transcription in H3K4me1/2 deposition at de novo enhancers that is independent of potential functions of the resulting eRNA transcripts.

引用

页码：310 / 325

页数：16

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