Crystal structure of the trithorax group protein ASH2L reveals a forkhead-like DNA binding domain

Sabina Sarvan; Vanja Avdic; Veronique Tremblay; Chandra Prakash Chaturvedi; Pamela Zhang; Sylvain Lanouette; Alexandre Blais; Joseph S. Brunzelle; Marjorie Brand; Jean François Couture

doi:10.1038/nsmb.2093

Crystal structure of the trithorax group protein ASH2L reveals a forkhead-like DNA binding domain

Sabina Sarvan, Vanja Avdic, Veronique Tremblay, Chandra Prakash Chaturvedi, Pamela Zhang, Sylvain Lanouette, Alexandre Blais, Joseph S. Brunzelle, Marjorie Brand, Jean François Couture^*

^*Corresponding author for this work

Pharmacology

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

35 Scopus citations

Abstract

Absent, small or homeotic discs-like 2 (ASH2L) is a trithorax group (TrxG) protein and a regulatory subunit of the SET1 family of lysine methyltransferases. Here we report that ASH2L binds DNA using a forkhead-like helix-wing-helix (HWH) domain. In vivo, the ASH2L HWH domain is required for binding to the -globin locus control region, histone H3 Lys4 (H3K4) trimethylation and maximal expression of the globin gene (Hbb-1), validating the functional importance of the ASH2L DNA binding domain.

Original language	English (US)
Pages (from-to)	857-859
Number of pages	3
Journal	Nature Structural and Molecular Biology
Volume	18
Issue number	7
DOIs	https://doi.org/10.1038/nsmb.2093
State	Published - Jul 2011

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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@article{71d9ac499d5344b18eb1a461af1e1585,

title = "Crystal structure of the trithorax group protein ASH2L reveals a forkhead-like DNA binding domain",

abstract = "Absent, small or homeotic discs-like 2 (ASH2L) is a trithorax group (TrxG) protein and a regulatory subunit of the SET1 family of lysine methyltransferases. Here we report that ASH2L binds DNA using a forkhead-like helix-wing-helix (HWH) domain. In vivo, the ASH2L HWH domain is required for binding to the -globin locus control region, histone H3 Lys4 (H3K4) trimethylation and maximal expression of the globin gene (Hbb-1), validating the functional importance of the ASH2L DNA binding domain.",

author = "Sabina Sarvan and Vanja Avdic and Veronique Tremblay and Chaturvedi, {Chandra Prakash} and Pamela Zhang and Sylvain Lanouette and Alexandre Blais and Brunzelle, {Joseph S.} and Marjorie Brand and Couture, {Jean Fran{\c c}ois}",

note = "Funding Information: We wish to thank J. Dilworth (Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute) for the Ash2L antibody and other reagents. We are highly indebted to R.C. Trievel, who facilitated part of this work. This work was supported by Canadian Institutes of Health Research (CIHR) grants to J.-F.C. (191666) and M.B. (MOP-89834). J.-F.C. holds a Canada Research Chair in Structural Biology and Epigenetics. P.Z. is sponsored by a Natural Sciences and Engineering Research Council of Canada (NSERC) fellowship. C.-P.C. is supported by a CIHR/Thalassemia Foundation of Canada postdoctoral fellowship.",

year = "2011",

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doi = "10.1038/nsmb.2093",

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AU - Sarvan, Sabina

AU - Avdic, Vanja

AU - Tremblay, Veronique

AU - Chaturvedi, Chandra Prakash

AU - Zhang, Pamela

AU - Lanouette, Sylvain

AU - Blais, Alexandre

AU - Brunzelle, Joseph S.

AU - Brand, Marjorie

AU - Couture, Jean François

N1 - Funding Information: We wish to thank J. Dilworth (Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute) for the Ash2L antibody and other reagents. We are highly indebted to R.C. Trievel, who facilitated part of this work. This work was supported by Canadian Institutes of Health Research (CIHR) grants to J.-F.C. (191666) and M.B. (MOP-89834). J.-F.C. holds a Canada Research Chair in Structural Biology and Epigenetics. P.Z. is sponsored by a Natural Sciences and Engineering Research Council of Canada (NSERC) fellowship. C.-P.C. is supported by a CIHR/Thalassemia Foundation of Canada postdoctoral fellowship.

PY - 2011/7

Y1 - 2011/7

N2 - Absent, small or homeotic discs-like 2 (ASH2L) is a trithorax group (TrxG) protein and a regulatory subunit of the SET1 family of lysine methyltransferases. Here we report that ASH2L binds DNA using a forkhead-like helix-wing-helix (HWH) domain. In vivo, the ASH2L HWH domain is required for binding to the -globin locus control region, histone H3 Lys4 (H3K4) trimethylation and maximal expression of the globin gene (Hbb-1), validating the functional importance of the ASH2L DNA binding domain.

AB - Absent, small or homeotic discs-like 2 (ASH2L) is a trithorax group (TrxG) protein and a regulatory subunit of the SET1 family of lysine methyltransferases. Here we report that ASH2L binds DNA using a forkhead-like helix-wing-helix (HWH) domain. In vivo, the ASH2L HWH domain is required for binding to the -globin locus control region, histone H3 Lys4 (H3K4) trimethylation and maximal expression of the globin gene (Hbb-1), validating the functional importance of the ASH2L DNA binding domain.

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Crystal structure of the trithorax group protein ASH2L reveals a forkhead-like DNA binding domain

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