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A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development

We have developed a general strategy for creating littermates bearing either a tissue-specific point mutation or deletion in any target gene, and used the method to dissect the roles of Brg, the ATPase subunit of the chromatin-remodeling Brg-associated factor (BAF) complex, in early thymocyte develo...

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Detalles Bibliográficos
Autores principales: Jani, Anant, Wan, Mimi, Zhang, Jianmin, Cui, Kairong, Wu, Jie, Preston-Hurlburt, Paula, Khatri, Rohini, Zhao, Keji, Chi, Tian
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585832/
https://www.ncbi.nlm.nih.gov/pubmed/18955569
http://dx.doi.org/10.1084/jem.20080938
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author Jani, Anant
Wan, Mimi
Zhang, Jianmin
Cui, Kairong
Wu, Jie
Preston-Hurlburt, Paula
Khatri, Rohini
Zhao, Keji
Chi, Tian
author_facet Jani, Anant
Wan, Mimi
Zhang, Jianmin
Cui, Kairong
Wu, Jie
Preston-Hurlburt, Paula
Khatri, Rohini
Zhao, Keji
Chi, Tian
author_sort Jani, Anant
collection PubMed
description We have developed a general strategy for creating littermates bearing either a tissue-specific point mutation or deletion in any target gene, and used the method to dissect the roles of Brg, the ATPase subunit of the chromatin-remodeling Brg-associated factor (BAF) complex, in early thymocyte development. We found that a point mutation that inactivates the Brg ATPase recapitulates multiple defects previously described for Brg deletion (Chi, T.H., M. Wan, P.P. Lee, K. Akashi, D. Metzger, P. Chambon, C.B. Wilson, and G.R. Crabtree. 2003. Immunity. 19:169–182). However, the point mutant helps reveal unexpected roles of Brg in CD25 repression and CD4 activation. Surprisingly, CD4 activation occurs independently of the Brg ATPase and is perhaps mediated by physical interactions between Brg and the CD4 locus. Our study thus suggests that the BAF complex harbors novel activities that can be necessary and even sufficient for stimulating transcription from an endogenous chromatin template in the absence of Brg-dependent remodeling of that template. We conclude that conditional point mutants, rarely used in mammalian genetics, can help uncover important gene functions undetectable or overlooked in deletion mutants.
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spelling pubmed-25858322009-05-24 A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development Jani, Anant Wan, Mimi Zhang, Jianmin Cui, Kairong Wu, Jie Preston-Hurlburt, Paula Khatri, Rohini Zhao, Keji Chi, Tian J Exp Med Articles We have developed a general strategy for creating littermates bearing either a tissue-specific point mutation or deletion in any target gene, and used the method to dissect the roles of Brg, the ATPase subunit of the chromatin-remodeling Brg-associated factor (BAF) complex, in early thymocyte development. We found that a point mutation that inactivates the Brg ATPase recapitulates multiple defects previously described for Brg deletion (Chi, T.H., M. Wan, P.P. Lee, K. Akashi, D. Metzger, P. Chambon, C.B. Wilson, and G.R. Crabtree. 2003. Immunity. 19:169–182). However, the point mutant helps reveal unexpected roles of Brg in CD25 repression and CD4 activation. Surprisingly, CD4 activation occurs independently of the Brg ATPase and is perhaps mediated by physical interactions between Brg and the CD4 locus. Our study thus suggests that the BAF complex harbors novel activities that can be necessary and even sufficient for stimulating transcription from an endogenous chromatin template in the absence of Brg-dependent remodeling of that template. We conclude that conditional point mutants, rarely used in mammalian genetics, can help uncover important gene functions undetectable or overlooked in deletion mutants. The Rockefeller University Press 2008-11-24 /pmc/articles/PMC2585832/ /pubmed/18955569 http://dx.doi.org/10.1084/jem.20080938 Text en © 2008 Jani et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Articles
Jani, Anant
Wan, Mimi
Zhang, Jianmin
Cui, Kairong
Wu, Jie
Preston-Hurlburt, Paula
Khatri, Rohini
Zhao, Keji
Chi, Tian
A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development
title A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development
title_full A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development
title_fullStr A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development
title_full_unstemmed A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development
title_short A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development
title_sort novel genetic strategy reveals unexpected roles of the swi–snf–like chromatin-remodeling baf complex in thymocyte development
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585832/
https://www.ncbi.nlm.nih.gov/pubmed/18955569
http://dx.doi.org/10.1084/jem.20080938
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