MSL Complex Is Attracted to Genes Marked by H3K36 Trimethylation Using a Sequence-Independent Mechanism

Erica Larschan; Artyom A. Alekseyenko; Andrey A. Gortchakov; Shouyong Peng; Bing Li; Pok Yang; Jerry L. Workman; Peter J. Park; Mitzi I. Kuroda

doi:10.1016/j.molcel.2007.08.011

MSL Complex Is Attracted to Genes Marked by H3K36 Trimethylation Using a Sequence-Independent Mechanism

Erica Larschan, Artyom A. Alekseyenko, Andrey A. Gortchakov, Shouyong Peng, Bing Li, Pok Yang, Jerry L. Workman, Peter J. Park, Mitzi I. Kuroda

Research output: Contribution to journal › Article › peer-review

173 Scopus citations

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 ∼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.

Original language	English (US)
Pages (from-to)	121-133
Number of pages	13
Journal	Molecular cell
Volume	28
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2007.08.011
State	Published - Oct 12 2007

Keywords

DEVBIO
DNA

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2007.08.011

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@article{52205c580dac41c286581468affaa713,

title = "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 ∼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 = "DEVBIO, DNA",

author = "Erica Larschan and Alekseyenko, {Artyom A.} and Gortchakov, {Andrey A.} and Shouyong Peng and Bing Li and Pok Yang and Workman, {Jerry L.} and Park, {Peter J.} and Kuroda, {Mitzi I.}",

note = "Funding Information: Many thanks to F. Winston, T. Sural, and C. Wang for important comments on the manuscript; O. Lee and J. Racine for excellent technical assistance; and M. Gelbart-Carey and S. Buratowski for helpful ideas and suggestions. We are grateful to H. Saumweber for antibodies. This work was supported by the National Institutes of Health (GM45744 to M.I.K and GM67825 to P.J.P), a grant to E.L. (a Leukemia and Lymphoma Society Fellow, 5198-05), and the Howard Hughes Medical Institute (HHMI). B.L. and J.L.W. are supported by a grant from the National Institutes of Health and funding from the Stowers Institute for Medical Research. ",

year = "2007",

month = oct,

day = "12",

doi = "10.1016/j.molcel.2007.08.011",

language = "English (US)",

volume = "28",

pages = "121--133",

journal = "Molecular cell",

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publisher = "Cell Press",

number = "1",

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T1 - MSL Complex Is Attracted to Genes Marked by H3K36 Trimethylation Using a Sequence-Independent Mechanism

AU - Larschan, Erica

AU - Alekseyenko, Artyom A.

AU - Gortchakov, Andrey A.

AU - Peng, Shouyong

AU - Li, Bing

AU - Yang, Pok

AU - Workman, Jerry L.

AU - Park, Peter J.

AU - Kuroda, Mitzi I.

N1 - Funding Information: Many thanks to F. Winston, T. Sural, and C. Wang for important comments on the manuscript; O. Lee and J. Racine for excellent technical assistance; and M. Gelbart-Carey and S. Buratowski for helpful ideas and suggestions. We are grateful to H. Saumweber for antibodies. This work was supported by the National Institutes of Health (GM45744 to M.I.K and GM67825 to P.J.P), a grant to E.L. (a Leukemia and Lymphoma Society Fellow, 5198-05), and the Howard Hughes Medical Institute (HHMI). B.L. and J.L.W. are supported by a grant from the National Institutes of Health and funding from the Stowers Institute for Medical Research.

PY - 2007/10/12

Y1 - 2007/10/12

N2 - 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 ∼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.

AB - 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 ∼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.

KW - DEVBIO

KW - DNA

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JF - Molecular cell

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ER -

MSL Complex Is Attracted to Genes Marked by H3K36 Trimethylation Using a Sequence-Independent Mechanism

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