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PMID: 19029895 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The MSL3 chromodomain directs a key targeting step for dosage compensation of the Drosophila melanogaster X chromosome.

Nature structural & molecular biology ·Vol. 15 ·No. 12 ·2008-12-00 ·Pages 1318-25

Sural TH, Peng S, Li B, Workman JL, Park PJ, Kuroda MI

Abstract

The male-specific lethal (MSL) complex upregulates the single male X chromosome to achieve dosage compensation in Drosophila melanogaster. We have proposed that MSL recognition of specific entry sites on the X is followed by local targeting of active genes marked by histone H3 trimethylation (H3K36me3). Here we analyze the role of the MSL3 chromodomain in the second targeting step. Using ChIP-chip analysis, we find that MSL3 chromodomain mutants retain binding to chromatin entry sites but show a clear disruption in the full pattern of MSL targeting in vivo, consistent with a loss of spreading. Furthermore, when compared to wild type, chromodomain mutants lack preferential affinity for nucleosomes containing H3K36me3 in vitro. Our results support a model in which activating complexes, similarly to their silencing counterparts, use the nucleosomal binding specificity of their respective chromodomains to spread from initiation sites to flanking chromatin.

MeSH Terms
Amino Acid Substitution Animals Animals, Genetically Modified Drosophila Proteins/genetics,metabolism Drosophila melanogaster/genetics,growth & development,metabolism Electrophoretic Mobility Shift Assay Female Histones/metabolism Male Microarray Analysis Models, Biological Mutagenesis, Site-Directed Mutant Proteins/metabolism Mutation, Missense Nuclear Proteins/genetics,metabolism Protein Binding Sequence Deletion Transcription Factors/genetics,metabolism X Chromosome
Chemicals
Drosophila Proteins Histones Mutant Proteins Nuclear Proteins Transcription Factors msl-3 protein, Drosophila
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sural Tuba H
Harvard-Partners Center for Genetics and Genomics, Division of Genetics, Department of Medicine, Brigham & Women's Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Peng Shouyong
Li Bing
Workman Jerry L
Park Peter J
Kuroda Mitzi I
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1520
Published
2008-12-00
Epub
2008-00-23
Pages
1318-25
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC2636508
Subset
IM
Grants
NIGMS NIH HHS · GM47867 · United States
NIGMS NIH HHS · R37 GM047867 · United States
NIGMS NIH HHS · R37 GM045744 · United States
NIGMS NIH HHS · R37 GM045744-17 · United States
NIGMS NIH HHS · GM67825 · United States
NIGMS NIH HHS · R01 GM045744 · United States
NIGMS NIH HHS · GM45744 · United States
NIGMS NIH HHS · K25 GM067825 · United States
NIGMS NIH HHS · R01 GM047867 · United States
External Links
PubMed source DOI: 10.1038/nsmb.1520 PMC Full Text View journal details
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