Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 205, Issue 12, Pages 2813-2825Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20080938
Keywords
-
Categories
Funding
- National Institutes of Health [R01AI063554-02]
- Anna Fuller Foundation
- Intramural Research Program of the National Heart, Lung, and Blood Institute/National Institutes of Health
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available