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MSL complex is attracted to genes marked by H3K36 trimethylation using a sequence-independent mechanism


ABSTRACT: In Drosophila, X chromosome dosage compensation requires the male-specific lethal (MSL) complex, which associates with actively transcribed genes on the single male X chromosome to upregulate transcription approximately 2-fold. We found that on the male X chromosome, or when MSL complex is ectopically localized to an autosome, histone H3K36 trimethylation (H3K36me3) is a strong predictor of MSL binding. We isolated mutants lacking Set2, the H3K36me3 methyltransferase, and found that Set2 is an essential gene in both sexes of Drosophila. In set2 mutant males, MSL complex maintains X specificity but exhibits reduced binding to target genes. Furthermore, recombinant MSL3 protein preferentially binds nucleosomes marked by H3K36me3 in vitro. Our results support a model in which MSL complex uses high-affinity sites to initially recognize the X chromosome and then associates with many of its targets through sequence-independent features of transcribed genes. Keywords: ChIP-chip ChIP-chip experiments were performed on custom Nimblegen arrays (GPL5636). Each array contained 388,000 oligonucleotide probes covering all of the X and the 2L chromosomes, with a 100 bp resolution (50mer probes with 50 bp gaps). The design was based on FlyBase 3.2. For the superspreading experiments, an additional array was used that contains the entire X chromosome and 3R (GPL5660). MSL complex binding sites on both arrays are the same and signal on the 3R chromosome was at background level.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Peter Park 

PROVIDER: E-GEOD-8557 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MSL complex is attracted to genes marked by H3K36 trimethylation using a sequence-independent mechanism.

Larschan Erica E   Alekseyenko Artyom A AA   Gortchakov Andrey A AA   Peng Shouyong S   Li Bing B   Yang Pok P   Workman Jerry L JL   Park Peter J PJ   Kuroda Mitzi I MI  

Molecular cell 20071001 1


In Drosophila, X chromosome dosage compensation requires the male-specific lethal (MSL) complex, which associates with actively transcribed genes on the single male X chromosome to upregulate transcription approximately 2-fold. We found that on the male X chromosome, or when MSL complex is ectopically localized to an autosome, histone H3K36 trimethylation (H3K36me3) is a strong predictor of MSL binding. We isolated mutants lacking Set2, the H3K36me3 methyltransferase, and found that Set2 is an e  ...[more]

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