TIF1γ Controls Erythroid Cell Fate by Regulating Transcription Elongation

被引:179
作者
Bai, Xiaoying [1 ,2 ,3 ]
Kim, Jonghwan [1 ,3 ,4 ]
Yang, Zhongan [5 ]
Jurynec, Michael J. [6 ]
Akie, Thomas E. [3 ]
Lee, Joseph [1 ,2 ,3 ]
LeBlanc, Jocelyn [1 ,2 ,3 ]
Sessa, Anna [1 ,2 ,3 ]
Jiang, Hong [5 ]
DiBiase, Anthony [1 ,2 ,3 ]
Zhou, Yi [1 ,2 ,3 ]
Grunwald, David J. [6 ]
Lin, Shuo [5 ]
Cantor, Alan B. [3 ]
Orkin, Stuart H. [1 ,3 ,4 ]
Zon, Leonard I. [1 ,2 ,3 ]
机构
[1] Howard Hughes Med Inst, Boston, MA 02115 USA
[2] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Div Hematol Oncol,Childrens Hosp Boston, Boston, MA 02115 USA
[4] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[5] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA
[6] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA
基金
美国国家卫生研究院;
关键词
POLYMERASE-II ELONGATION; RNA-POLYMERASE; P-TEFB; PAF1; COMPLEX; GATA-1; GENES; DSIF; IDENTIFICATION; HEMATOPOIESIS; METHYLATION;
D O I
10.1016/j.cell.2010.05.028
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 genome-wide studies have demonstrated that pausing of RNA polymerase II (Pol II) occurred on many vertebrate genes. By genetic studies in the zebrafish tif1 gamma mutant moonshine we found that loss of function of Pol II-associated factors PAF or DSIF rescued erythroid gene transcription in tif1 gamma-deficient animals. Biochemical analysis established physical interactions among TIF1 gamma, the blood-specific SCL transcription complex, and the positive elongation factors p-TEFb and FACT. Chromatin immunoprecipitation assays in human CD34(+) cells supported a TIF1 gamma-dependent recruitment of positive elongation factors to erythroid genes to promote transcription elongation by counteracting Pol II pausing. Our study establishes a mechanism for regulating tissue cell fate and differentiation through transcription elongation.
引用
收藏
页码:133 / 143
页数:11
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