Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes

Diana Vradii, Stefan Wagner, Diem N. Doan, Jeffrey A. Nickerson, Martin Montecino, Jane B. Lian, Janet L. Stein, Andre J van Wijnen, Anthony N. Imbalzano, Gary S. Stein

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Many mammalian SWI/SNF complexes use Brahma-related gene 1 (Brg1) as a catalytic subunit to remodel nucleosomes for transcription regulation. In several mesenchymal cells and tissues, expression of a defective Brg1 protein negates the normal activity of the SWI/SNF complex and delays or blocks differentiation. To investigate the role of SWI/SNF complexes during myelopoiesis, we stably expressed a dominant negative (dn) Brg1 mutant in the myeloid lineage. Forced expression of dnBrg1 in IL-3-dependent murine 32Dc13 myeloid progenitor cells results in a profound delay in the granulocyte-colony stimulating factor (G-CSF) induced granulocytic maturation. These cells also exhibit a significant decrease in the expression of both CD11b and Gr-1 surface receptors, which are normally upregulated during granulopoiesis, and show sustained expression of myeloperoxidase, which is synthesized primarily during the promyelocytic (blast) stage of myeloid development. Thus, dnBrg1 expression causes a developmental block at the promyelocytic/metamyelocytic stage of myeloid differentiation. Our findings indicate that the normal chromatin remodeling function of Brg1 is necessary for the G-CSF dependent differentiation of myeloid cells towards the granulocytic lineage. This dependency on Brg1 may reflect a stringent requirement for chromatin remodeling at a critical stage of hematopoietic cell maturation.

Original languageEnglish (US)
Pages (from-to)112-118
Number of pages7
JournalJournal of Cellular Physiology
Volume206
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Fingerprint

Chromatin Assembly and Disassembly
Granulocytes
Chromatin
Adenosine Triphosphatases
Genes
Granulocyte Colony-Stimulating Factor
Myelopoiesis
Myeloid Progenitor Cells
Nucleosomes
Interleukin-3
Myeloid Cells
Peroxidase
Transcription
Catalytic Domain
Cells
Tissue
Proteins

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Vradii, D., Wagner, S., Doan, D. N., Nickerson, J. A., Montecino, M., Lian, J. B., ... Stein, G. S. (2006). Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes. Journal of Cellular Physiology, 206(1), 112-118. https://doi.org/10.1002/jcp.20432

Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes. / Vradii, Diana; Wagner, Stefan; Doan, Diem N.; Nickerson, Jeffrey A.; Montecino, Martin; Lian, Jane B.; Stein, Janet L.; van Wijnen, Andre J; Imbalzano, Anthony N.; Stein, Gary S.

In: Journal of Cellular Physiology, Vol. 206, No. 1, 01.2006, p. 112-118.

Research output: Contribution to journalArticle

Vradii, D, Wagner, S, Doan, DN, Nickerson, JA, Montecino, M, Lian, JB, Stein, JL, van Wijnen, AJ, Imbalzano, AN & Stein, GS 2006, 'Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes', Journal of Cellular Physiology, vol. 206, no. 1, pp. 112-118. https://doi.org/10.1002/jcp.20432
Vradii, Diana ; Wagner, Stefan ; Doan, Diem N. ; Nickerson, Jeffrey A. ; Montecino, Martin ; Lian, Jane B. ; Stein, Janet L. ; van Wijnen, Andre J ; Imbalzano, Anthony N. ; Stein, Gary S. / Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes. In: Journal of Cellular Physiology. 2006 ; Vol. 206, No. 1. pp. 112-118.
@article{d2fadea0934e4e4183ae649b4d2b7868,
title = "Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes",
abstract = "Many mammalian SWI/SNF complexes use Brahma-related gene 1 (Brg1) as a catalytic subunit to remodel nucleosomes for transcription regulation. In several mesenchymal cells and tissues, expression of a defective Brg1 protein negates the normal activity of the SWI/SNF complex and delays or blocks differentiation. To investigate the role of SWI/SNF complexes during myelopoiesis, we stably expressed a dominant negative (dn) Brg1 mutant in the myeloid lineage. Forced expression of dnBrg1 in IL-3-dependent murine 32Dc13 myeloid progenitor cells results in a profound delay in the granulocyte-colony stimulating factor (G-CSF) induced granulocytic maturation. These cells also exhibit a significant decrease in the expression of both CD11b and Gr-1 surface receptors, which are normally upregulated during granulopoiesis, and show sustained expression of myeloperoxidase, which is synthesized primarily during the promyelocytic (blast) stage of myeloid development. Thus, dnBrg1 expression causes a developmental block at the promyelocytic/metamyelocytic stage of myeloid differentiation. Our findings indicate that the normal chromatin remodeling function of Brg1 is necessary for the G-CSF dependent differentiation of myeloid cells towards the granulocytic lineage. This dependency on Brg1 may reflect a stringent requirement for chromatin remodeling at a critical stage of hematopoietic cell maturation.",
author = "Diana Vradii and Stefan Wagner and Doan, {Diem N.} and Nickerson, {Jeffrey A.} and Martin Montecino and Lian, {Jane B.} and Stein, {Janet L.} and {van Wijnen}, {Andre J} and Imbalzano, {Anthony N.} and Stein, {Gary S.}",
year = "2006",
month = "1",
doi = "10.1002/jcp.20432",
language = "English (US)",
volume = "206",
pages = "112--118",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes

AU - Vradii, Diana

AU - Wagner, Stefan

AU - Doan, Diem N.

AU - Nickerson, Jeffrey A.

AU - Montecino, Martin

AU - Lian, Jane B.

AU - Stein, Janet L.

AU - van Wijnen, Andre J

AU - Imbalzano, Anthony N.

AU - Stein, Gary S.

PY - 2006/1

Y1 - 2006/1

N2 - Many mammalian SWI/SNF complexes use Brahma-related gene 1 (Brg1) as a catalytic subunit to remodel nucleosomes for transcription regulation. In several mesenchymal cells and tissues, expression of a defective Brg1 protein negates the normal activity of the SWI/SNF complex and delays or blocks differentiation. To investigate the role of SWI/SNF complexes during myelopoiesis, we stably expressed a dominant negative (dn) Brg1 mutant in the myeloid lineage. Forced expression of dnBrg1 in IL-3-dependent murine 32Dc13 myeloid progenitor cells results in a profound delay in the granulocyte-colony stimulating factor (G-CSF) induced granulocytic maturation. These cells also exhibit a significant decrease in the expression of both CD11b and Gr-1 surface receptors, which are normally upregulated during granulopoiesis, and show sustained expression of myeloperoxidase, which is synthesized primarily during the promyelocytic (blast) stage of myeloid development. Thus, dnBrg1 expression causes a developmental block at the promyelocytic/metamyelocytic stage of myeloid differentiation. Our findings indicate that the normal chromatin remodeling function of Brg1 is necessary for the G-CSF dependent differentiation of myeloid cells towards the granulocytic lineage. This dependency on Brg1 may reflect a stringent requirement for chromatin remodeling at a critical stage of hematopoietic cell maturation.

AB - Many mammalian SWI/SNF complexes use Brahma-related gene 1 (Brg1) as a catalytic subunit to remodel nucleosomes for transcription regulation. In several mesenchymal cells and tissues, expression of a defective Brg1 protein negates the normal activity of the SWI/SNF complex and delays or blocks differentiation. To investigate the role of SWI/SNF complexes during myelopoiesis, we stably expressed a dominant negative (dn) Brg1 mutant in the myeloid lineage. Forced expression of dnBrg1 in IL-3-dependent murine 32Dc13 myeloid progenitor cells results in a profound delay in the granulocyte-colony stimulating factor (G-CSF) induced granulocytic maturation. These cells also exhibit a significant decrease in the expression of both CD11b and Gr-1 surface receptors, which are normally upregulated during granulopoiesis, and show sustained expression of myeloperoxidase, which is synthesized primarily during the promyelocytic (blast) stage of myeloid development. Thus, dnBrg1 expression causes a developmental block at the promyelocytic/metamyelocytic stage of myeloid differentiation. Our findings indicate that the normal chromatin remodeling function of Brg1 is necessary for the G-CSF dependent differentiation of myeloid cells towards the granulocytic lineage. This dependency on Brg1 may reflect a stringent requirement for chromatin remodeling at a critical stage of hematopoietic cell maturation.

UR - http://www.scopus.com/inward/record.url?scp=28444464059&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28444464059&partnerID=8YFLogxK

U2 - 10.1002/jcp.20432

DO - 10.1002/jcp.20432

M3 - Article

C2 - 15965950

AN - SCOPUS:28444464059

VL - 206

SP - 112

EP - 118

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 1

ER -