BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells

Matthias D. Kaeser, Aaron Aslanian, Meng Qiu Dong, John R. Yates, Beverly Emerson

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

The composition of chromatin-remodeling complexes dictates how these enzymes control transcriptional programs and cellular identity. In the present study we investigated the composition of SWI/SNF complexes in embryonic stem cells (ESCs). In contrast to differentiated cells, ESCs have a biased incorporation of certain paralogous SWI/SNF subunits with low levels of BRM, BAF170, and ARID1B. Upon differentiation, the expression of these subunits increases, resulting in a higher diversity of compositionally distinct SWI/SNF enzymes. We also identified BRD7 as a novel component of the Polybromo-associated BRG1-associated factor (PBAF) complex in both ESCs and differentiated cells. Using short hairpin RNA-mediated depletion of BRG1, we showed that SWI/SNF can function as both a repressor and an activator in pluripotent cells, regulating expression of developmental modifiers and signaling components such as Nodal, ADAMTS1, BMI-1, CRABP1, and thyroid releasing hormone. Knockdown studies of PBAF-specific BRD7 and of a signature subunit within the BAF complex, ARID1A, showed that these two subcomplexes affect SWI/SNF target genes differentially, in some cases even antagonistically. This may be due to their different biochemical properties. Finally we examined the role of SWI/SNF in regulating its target genes during differentiation. We found that SWI/SNF affects recruitment of components of the preinitiation complex in a promoter-specific manner to modulate transcription positively or negatively. Taken together, our results provide insight into the function of compositionally diverse SWI/SNF enzymes that underlie their inherent gene-specific mode of action.

Original languageEnglish (US)
Pages (from-to)32254-32263
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number47
DOIs
StatePublished - Nov 21 2008
Externally publishedYes

Fingerprint

Embryonic Stem Cells
Stem cells
Transcriptional Activation
Genes
Chemical activation
Enzymes
Chromatin Assembly and Disassembly
Transcription
Chemical analysis
Thyroid Hormones
Small Interfering RNA
Chromatin
Hormones

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells. / Kaeser, Matthias D.; Aslanian, Aaron; Dong, Meng Qiu; Yates, John R.; Emerson, Beverly.

In: Journal of Biological Chemistry, Vol. 283, No. 47, 21.11.2008, p. 32254-32263.

Research output: Contribution to journalArticle

Kaeser, Matthias D. ; Aslanian, Aaron ; Dong, Meng Qiu ; Yates, John R. ; Emerson, Beverly. / BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 47. pp. 32254-32263.
@article{08d15bc4c3ea4f25a73f29df2c012f4d,
title = "BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells",
abstract = "The composition of chromatin-remodeling complexes dictates how these enzymes control transcriptional programs and cellular identity. In the present study we investigated the composition of SWI/SNF complexes in embryonic stem cells (ESCs). In contrast to differentiated cells, ESCs have a biased incorporation of certain paralogous SWI/SNF subunits with low levels of BRM, BAF170, and ARID1B. Upon differentiation, the expression of these subunits increases, resulting in a higher diversity of compositionally distinct SWI/SNF enzymes. We also identified BRD7 as a novel component of the Polybromo-associated BRG1-associated factor (PBAF) complex in both ESCs and differentiated cells. Using short hairpin RNA-mediated depletion of BRG1, we showed that SWI/SNF can function as both a repressor and an activator in pluripotent cells, regulating expression of developmental modifiers and signaling components such as Nodal, ADAMTS1, BMI-1, CRABP1, and thyroid releasing hormone. Knockdown studies of PBAF-specific BRD7 and of a signature subunit within the BAF complex, ARID1A, showed that these two subcomplexes affect SWI/SNF target genes differentially, in some cases even antagonistically. This may be due to their different biochemical properties. Finally we examined the role of SWI/SNF in regulating its target genes during differentiation. We found that SWI/SNF affects recruitment of components of the preinitiation complex in a promoter-specific manner to modulate transcription positively or negatively. Taken together, our results provide insight into the function of compositionally diverse SWI/SNF enzymes that underlie their inherent gene-specific mode of action.",
author = "Kaeser, {Matthias D.} and Aaron Aslanian and Dong, {Meng Qiu} and Yates, {John R.} and Beverly Emerson",
year = "2008",
month = "11",
day = "21",
doi = "10.1074/jbc.M806061200",
language = "English (US)",
volume = "283",
pages = "32254--32263",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "47",

}

TY - JOUR

T1 - BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells

AU - Kaeser, Matthias D.

AU - Aslanian, Aaron

AU - Dong, Meng Qiu

AU - Yates, John R.

AU - Emerson, Beverly

PY - 2008/11/21

Y1 - 2008/11/21

N2 - The composition of chromatin-remodeling complexes dictates how these enzymes control transcriptional programs and cellular identity. In the present study we investigated the composition of SWI/SNF complexes in embryonic stem cells (ESCs). In contrast to differentiated cells, ESCs have a biased incorporation of certain paralogous SWI/SNF subunits with low levels of BRM, BAF170, and ARID1B. Upon differentiation, the expression of these subunits increases, resulting in a higher diversity of compositionally distinct SWI/SNF enzymes. We also identified BRD7 as a novel component of the Polybromo-associated BRG1-associated factor (PBAF) complex in both ESCs and differentiated cells. Using short hairpin RNA-mediated depletion of BRG1, we showed that SWI/SNF can function as both a repressor and an activator in pluripotent cells, regulating expression of developmental modifiers and signaling components such as Nodal, ADAMTS1, BMI-1, CRABP1, and thyroid releasing hormone. Knockdown studies of PBAF-specific BRD7 and of a signature subunit within the BAF complex, ARID1A, showed that these two subcomplexes affect SWI/SNF target genes differentially, in some cases even antagonistically. This may be due to their different biochemical properties. Finally we examined the role of SWI/SNF in regulating its target genes during differentiation. We found that SWI/SNF affects recruitment of components of the preinitiation complex in a promoter-specific manner to modulate transcription positively or negatively. Taken together, our results provide insight into the function of compositionally diverse SWI/SNF enzymes that underlie their inherent gene-specific mode of action.

AB - The composition of chromatin-remodeling complexes dictates how these enzymes control transcriptional programs and cellular identity. In the present study we investigated the composition of SWI/SNF complexes in embryonic stem cells (ESCs). In contrast to differentiated cells, ESCs have a biased incorporation of certain paralogous SWI/SNF subunits with low levels of BRM, BAF170, and ARID1B. Upon differentiation, the expression of these subunits increases, resulting in a higher diversity of compositionally distinct SWI/SNF enzymes. We also identified BRD7 as a novel component of the Polybromo-associated BRG1-associated factor (PBAF) complex in both ESCs and differentiated cells. Using short hairpin RNA-mediated depletion of BRG1, we showed that SWI/SNF can function as both a repressor and an activator in pluripotent cells, regulating expression of developmental modifiers and signaling components such as Nodal, ADAMTS1, BMI-1, CRABP1, and thyroid releasing hormone. Knockdown studies of PBAF-specific BRD7 and of a signature subunit within the BAF complex, ARID1A, showed that these two subcomplexes affect SWI/SNF target genes differentially, in some cases even antagonistically. This may be due to their different biochemical properties. Finally we examined the role of SWI/SNF in regulating its target genes during differentiation. We found that SWI/SNF affects recruitment of components of the preinitiation complex in a promoter-specific manner to modulate transcription positively or negatively. Taken together, our results provide insight into the function of compositionally diverse SWI/SNF enzymes that underlie their inherent gene-specific mode of action.

UR - http://www.scopus.com/inward/record.url?scp=57749105431&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57749105431&partnerID=8YFLogxK

U2 - 10.1074/jbc.M806061200

DO - 10.1074/jbc.M806061200

M3 - Article

C2 - 18809673

AN - SCOPUS:57749105431

VL - 283

SP - 32254

EP - 32263

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 47

ER -