MAP3K4/CBP-Regulated H2B Acetylation Controls Epithelial-Mesenchymal Transition in Trophoblast Stem Cells

被引：107

作者：

Abell, Amy N. ^{[1
,2
]}

Jordan, Nicole Vincent ^{[1
,2
]}

Huang, Weichun ^{[7
]}

Prat, Aleix ^{[2
,3
]}

Midland, Alicia A. ^{[5
,6
]}

Johnson, Nancy L. ^{[1
,2
]}

Granger, Deborah A. ^{[1
,2
]}

Mieczkowski, Piotr A. ^{[2
,3
,4
]}

Perou, Charles M. ^{[2
,3
]}

Gomez, Shawn M. ^{[5
,6
]}

Li, Leping ^{[7
]}

Johnson, Gary L. ^{[1
,2
]}

机构：

[1] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[3] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA

[4] Univ N Carolina, Sch Med, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Sch Med, Dept Biomed Engn, Chapel Hill, NC 27599 USA

[6] Univ N Carolina, Sch Med, Curriculum Bioinformat & Computat Biol, Chapel Hill, NC 27599 USA

[7] Natl Inst Environm Hlth Sci RTP, Biostat Branch, Res Triangle Pk, NC 27709 USA

来源：

CELL STEM CELL | 2011年 / 8卷 / 05期

关键词：

BREAST-CANCER; MOUSE EMBRYO; SELF-RENEWAL; MECHANISMS; DISEASE; KINASE; LINES;

D O I：

10.1016/j.stem.2011.03.008

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Epithelial stem cells self-renew while maintaining multipotency, but the dependence of stem cell properties on maintenance of the epithelial phenotype is unclear. We previously showed that trophoblast stem (TS) cells lacking the protein kinase MAP3K4 maintain properties of both sternness and epithelial-mesenchymal transition (EMT). Here, we show that MAP3K4 controls the activity of the histone acetyltransferase CBP, and that acetylation of histones H2A and H2B by CBP is required to maintain the epithelial phenotype. Combined loss of MAP3K4/CBP activity represses expression of epithelial genes and causes IS cells to undergo EMT while maintaining their self-renewal and multipotency properties. The expression profile of MAP3K4-deficient TS cells defines an H2B acetylation-regulated gene signature that closely overlaps with that of human breast cancer cells. Taken together, our data define an epigenetic switch that maintains the epithelial phenotype in TS cells and reveals previously unrecognized genes potentially contributing to breast cancer.

引用

页码：525 / 537

页数：13

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