Sequential roles of Brg, the ATPase subunit of BAF chromatin remodeling complexes, in thymocyte development.
T cells develop through distinct stages directed by a series of signals. We explored the roles of SWI/SNF-like BAF chromatin remodeling complexes in this process by progressive deletion of the ATPase subunit, Brg, through successive stages of early T cell development. Brg-deficient cells were blocked at each of the developmental transitions examined. Bcl-xL overexpression suppressed cell death without relieving the developmental blockades, leading to the accumulation of Brg-deleted cells that were unexpectedly cell cycle arrested. These defects resulted partly from the disruptions of pre-TCR and potentially Wnt signaling pathways controlling the expression of genes such as c-Kit and c-Myc critical for continued development. Our studies indicate that BAF complexes dynamically remodel chromatin to propel sequential developmental transitions in response to external signals.
Chi
Tian H
TH
Departments of Pathology and Developmental Biology, Howard Hughes Medical Institute, Stanford University Medical School, Palo Alto, California 94305, USA.
Wan
Mimi
M
Lee
Peggy P
PP
Akashi
Koichi
K
Metzger
Daniel
D
Chambon
Pierre
P
Wilson
Christopher B
CB
Crabtree
Gerald R
GR
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism*; D004265:DNA Helicases; D016259:Genes, myc; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009691:Nucleic Acid Denaturation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D002843:Chromatin; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C499503:Smarca2 protein, mouse; D014157:Transcription Factors; D051020:bcl-X Protein; D019009:Proto-Oncogene Proteins c-kit; D000251:Adenosine Triphosphatases; C513194:Smarca4 protein, mouse; D004265:DNA Helicases