Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly

Wei Jian, Bowen Yan, Suming Huang, Yi Qiu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Histone acetyltransferases and histone deacetylases (HDACs) are important epigenetic coregulators. It has been thought that HDACs associate with corepressor complexes and repress gene transcription; however, in this study, we have found that PU.1—a key master regulator for hematopoietic self-renewal and lineage specification—requires HDAC activity for gene activation. Deregulated PU.1 gene expression is linked to dysre-gulated hematopoiesis and the development of leukemia. In this study, we used erythroid differentiation as a model to analyze how the PU.1 gene is regulated. We found that active HDAC1 is directly recruited to active PU.1 promoter in progenitor cells, whereas acetylated HDAC1, which is inactive, is on the silenced PU.1 promoter in differentiated erythroid cells. We then studied the mechanism of HDAC1-mediated activation. We discovered that HDAC1 activates PU.1 gene transcription via deacetylation of TATA-binding protein–associated factor 9 (TAF9), a component in the transcription factor IID (TFIID) complex. Treatment with HDAC inhibitor results in an increase in TAF9 acetylation. Acetylated TAF9 does not bind to the PU.1 gene promoter and subsequently leads to the disassociation of the TFIID complex and transcription repression. Thus, these results demonstrate a key role for HDAC1 in PU.1 gene transcription and, more importantly, uncover a novel mechanism of TFIID recruitment and gene activation.

Original languageEnglish (US)
Pages (from-to)4104-4116
Number of pages13
JournalFASEB Journal
Volume31
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Histone Deacetylase 1
Transcription Factor TFIID
Transcription
Histone Deacetylases
Genes
Transcriptional Activation
Chemical activation
Histone Acetyltransferases
Co-Repressor Proteins
Erythroid Cells
Hematopoiesis
Acetylation
Epigenomics
Leukemia
Stem Cells
Gene expression
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

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title = "Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly",
abstract = "Histone acetyltransferases and histone deacetylases (HDACs) are important epigenetic coregulators. It has been thought that HDACs associate with corepressor complexes and repress gene transcription; however, in this study, we have found that PU.1—a key master regulator for hematopoietic self-renewal and lineage specification—requires HDAC activity for gene activation. Deregulated PU.1 gene expression is linked to dysre-gulated hematopoiesis and the development of leukemia. In this study, we used erythroid differentiation as a model to analyze how the PU.1 gene is regulated. We found that active HDAC1 is directly recruited to active PU.1 promoter in progenitor cells, whereas acetylated HDAC1, which is inactive, is on the silenced PU.1 promoter in differentiated erythroid cells. We then studied the mechanism of HDAC1-mediated activation. We discovered that HDAC1 activates PU.1 gene transcription via deacetylation of TATA-binding protein–associated factor 9 (TAF9), a component in the transcription factor IID (TFIID) complex. Treatment with HDAC inhibitor results in an increase in TAF9 acetylation. Acetylated TAF9 does not bind to the PU.1 gene promoter and subsequently leads to the disassociation of the TFIID complex and transcription repression. Thus, these results demonstrate a key role for HDAC1 in PU.1 gene transcription and, more importantly, uncover a novel mechanism of TFIID recruitment and gene activation.",
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Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly. / Jian, Wei; Yan, Bowen; Huang, Suming; Qiu, Yi.

In: FASEB Journal, Vol. 31, No. 9, 01.09.2017, p. 4104-4116.

Research output: Contribution to journalArticle

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