TIF1γ Controls Erythroid Cell Fate by Regulating Transcription Elongation

Xiaoying Bai; Jonghwan Kim; Zhongan Yang; Michael J. Jurynec; Thomas E. Akie; Joseph Lee; Jocelyn LeBlanc; Anna Sessa; Hong Jiang; Anthony DiBiase; Yi Zhou; David J. Grunwald; Shuo Lin; Alan B. Cantor; Stuart H. Orkin; Leonard I. Zon

doi:10.1016/j.cell.2010.05.028

TIF1γ Controls Erythroid Cell Fate by Regulating Transcription Elongation

Xiaoying Bai, Jonghwan Kim, Zhongan Yang, Michael J. Jurynec, Thomas E. Akie, Joseph Lee, Jocelyn LeBlanc, Anna Sessa, Hong Jiang, Anthony DiBiase, Yi Zhou, David J. Grunwald, Shuo Lin, Alan B. Cantor, Stuart H. Orkin, Leonard I. Zon

Research output: Contribution to journal › Article › peer-review

176 Scopus citations

Abstract

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 tif1γ mutant moonshine we found that loss of function of Pol II-associated factors PAF or DSIF rescued erythroid gene transcription in tif1γ-deficient animals. Biochemical analysis established physical interactions among TIF1γ, the blood-specific SCL transcription complex, and the positive elongation factors p-TEFb and FACT. Chromatin immunoprecipitation assays in human CD34⁺ cells supported a TIF1γ-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.

Original language	English (US)
Pages (from-to)	133-143
Number of pages	11
Journal	Cell
Volume	142
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2010.05.028
State	Published - Jul 2010

Keywords

Dev Bio
RNA

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2010.05.028

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@article{d335ed520cf247f686e24d8c875707f1,

title = "TIF1γ Controls Erythroid Cell Fate by Regulating Transcription Elongation",

abstract = "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 tif1γ mutant moonshine we found that loss of function of Pol II-associated factors PAF or DSIF rescued erythroid gene transcription in tif1γ-deficient animals. Biochemical analysis established physical interactions among TIF1γ, the blood-specific SCL transcription complex, and the positive elongation factors p-TEFb and FACT. Chromatin immunoprecipitation assays in human CD34+ cells supported a TIF1γ-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.",

keywords = "Dev Bio, RNA",

author = "Xiaoying Bai and Jonghwan Kim and Zhongan Yang and Jurynec, {Michael J.} and Akie, {Thomas E.} and Joseph Lee and Jocelyn LeBlanc and Anna Sessa and Hong Jiang and Anthony DiBiase and Yi Zhou and Grunwald, {David J.} and Shuo Lin and Cantor, {Alan B.} and Orkin, {Stuart H.} and Zon, {Leonard I.}",

note = "Funding Information: We thank Drs. H. Chen, S. Guo, S. Takada, E.H. Bresnick, and S.J. Brandt for providing regents, Y. Huang, A. Chen, and R. Mathieu for technical assistance. We are grateful to Drs. T.V. Bowman, C. Ceol, and R. White for helpful discussion and critical comments. This study was supported by National Institutes of Health grants 5PO1HL32262-28 and 5R37 DK55381-010. X. Bai and J. Kim are Howard Hughes Medical Institute (HHMI) research fellows. L.I. Zon and S.H. Orkin are HHMI investigators. L.I.Z. is a founder and stock holder of Fate, Inc. and a scientific advisor for Stemgent. ",

year = "2010",

month = jul,

doi = "10.1016/j.cell.2010.05.028",

language = "English (US)",

volume = "142",

pages = "133--143",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "1",

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TY - JOUR

T1 - TIF1γ Controls Erythroid Cell Fate by Regulating Transcription Elongation

AU - Bai, Xiaoying

AU - Kim, Jonghwan

AU - Yang, Zhongan

AU - Jurynec, Michael J.

AU - Akie, Thomas E.

AU - Lee, Joseph

AU - LeBlanc, Jocelyn

AU - Sessa, Anna

AU - Jiang, Hong

AU - DiBiase, Anthony

AU - Zhou, Yi

AU - Grunwald, David J.

AU - Lin, Shuo

AU - Cantor, Alan B.

AU - Orkin, Stuart H.

AU - Zon, Leonard I.

N1 - Funding Information: We thank Drs. H. Chen, S. Guo, S. Takada, E.H. Bresnick, and S.J. Brandt for providing regents, Y. Huang, A. Chen, and R. Mathieu for technical assistance. We are grateful to Drs. T.V. Bowman, C. Ceol, and R. White for helpful discussion and critical comments. This study was supported by National Institutes of Health grants 5PO1HL32262-28 and 5R37 DK55381-010. X. Bai and J. Kim are Howard Hughes Medical Institute (HHMI) research fellows. L.I. Zon and S.H. Orkin are HHMI investigators. L.I.Z. is a founder and stock holder of Fate, Inc. and a scientific advisor for Stemgent.

PY - 2010/7

Y1 - 2010/7

N2 - 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 tif1γ mutant moonshine we found that loss of function of Pol II-associated factors PAF or DSIF rescued erythroid gene transcription in tif1γ-deficient animals. Biochemical analysis established physical interactions among TIF1γ, the blood-specific SCL transcription complex, and the positive elongation factors p-TEFb and FACT. Chromatin immunoprecipitation assays in human CD34+ cells supported a TIF1γ-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.

AB - 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 tif1γ mutant moonshine we found that loss of function of Pol II-associated factors PAF or DSIF rescued erythroid gene transcription in tif1γ-deficient animals. Biochemical analysis established physical interactions among TIF1γ, the blood-specific SCL transcription complex, and the positive elongation factors p-TEFb and FACT. Chromatin immunoprecipitation assays in human CD34+ cells supported a TIF1γ-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.

KW - Dev Bio

KW - RNA

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JO - Cell

JF - Cell

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TIF1γ Controls Erythroid Cell Fate by Regulating Transcription Elongation

Abstract

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