A Wt1-Controlled Chromatin Switching Mechanism Underpins Tissue-Specific Wnt4 Activation and Repression

被引：116

作者：

Essafi, Abdelkader ^{[1
,2
]}

Webb, Anna ^{[1
,2
]}

Berry, Rachel L. ^{[1
,2
]}

Slight, Joan ^{[1
,2
]}

Burn, Sally F. ^{[1
,2
]}

Spraggon, Lee ^{[1
,2
]}

Velecela, Victor ^{[1
,2
]}

Martinez-Estrada, Ofelia M. ^{[1
,2
]}

Wiltshire, John H. ^{[1
,2
]}

Roberts, Stefan G. E. ^{[3
]}

Brownstein, David ^{[4
]}

Davies, Jamie A. ^{[5
]}

Hastie, Nicholas D. ^{[1
,2
]}

Hohenstein, Peter ^{[1
,2
]}

机构：

[1] Western Gen Hosp, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[2] Western Gen Hosp, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland

[3] SUNY Buffalo, Dept Biol Sci, Buffalo, NY 14260 USA

[4] Univ Edinburgh, Div Pathol, Comparat Pathol Core Facil, Queens Med Res Inst, Edinburgh EH16 4TJ, Midlothian, Scotland

[5] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland

来源：

DEVELOPMENTAL CELL | 2011年 / 21卷 / 03期

关键词：

RNA-POLYMERASE-II; WILMS-TUMOR GENE; EPITHELIAL TRANSFORMATION; METANEPHRIC MESENCHYME; DEVELOPING KIDNEY; SUPPRESSOR; EXPRESSION; WT1; TRANSCRIPTION; REVEALS;

D O I：

10.1016/j.devcel.2011.07.014

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Wt1 regulates the epithelial-mesenchymal transition (EMT) in the epicardium and the reverse process (MET) in kidney mesenchyme. The mechanisms underlying these reciprocal functions are unknown. Here, we show in both embryos and cultured cells that Wt1 regulates Wnt4 expression dichotomously. In kidney cells, Wt1 recruits Cbp and p300 as coactivators; in epicardial cells it enlists Basp1 as a corepressor. Surprisingly, in both tissues, Wt1 loss reciprocally switches the chromatin architecture of the entire Ctcf-bounded Wnt4 locus, but not the flanking regions; we term this mode of action "chromatin flip-flop." Ctcf and cohesin are dispensable for Wt1-mediated chromatin flip-flop but essential for maintaining the insulating boundaries. This work demonstrates that a developmental regulator coordinates chromatin boundaries with the transcriptional competence of the flanked region. These findings also have implications for hierarchical transcriptional regulation in development and disease.

引用

页码：559 / 574

页数：16

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