Related Experiment Videos
Modulation of ISWI function by site-specific histone acetylation.
Davide F V Corona1, Cedric R Clapier, Peter B Becker
1Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, USA.
EMBO Reports
|March 8, 2002
Summary
Mutations in the ISWI protein disrupt male X chromosome structure. Blocking H4K16 acetylation rescues these defects, suggesting H4K16 acetylation counteracts ISWI
Area of Science:
- Molecular Biology
- Genetics
- Chromatin Biology
Background:
- ISWI is a chromatin remodeling ATPase crucial for genome organization.
- Dosage compensation in Drosophila males involves increased transcription and H4K16 acetylation on the X chromosome.
Purpose of the Study:
- To investigate the functional relationship between ISWI and H4K16 acetylation in regulating X chromosome architecture.
- To determine if H4K16 acetylation directly impacts ISWI's chromatin remodeling activity.
Main Methods:
- Genetic manipulation of ISWI and H4K16 acetylation levels in Drosophila.
- Phenotypic analysis of X chromosome structure and gene expression.
- Biochemical assays, including peptide competition, to assess ISWI-substrate interactions.
Main Results:
- Loss of ISWI function causes X chromosome defects that are suppressed by blocking H4K16 acetylation.
- Forced H4K16 acetylation in ISWI mutant females mimics male X chromosome defects.
- Increased MOF expression exacerbates ISWI loss-of-function phenotypes.
- H4K16 acetylation impairs ISWI's ability to bind its chromatin substrate.
Conclusions:
- H4K16 acetylation directly antagonizes ISWI-mediated chromatin compaction.
- This acetylation acts as a key regulator of X chromosome structure and function, interacting with chromatin remodelers.