Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are differentially required for histone H3 Lys 4 methylation in embryos and adult germ cells

TY - JOUR

T1 - Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are differentially required for histone H3 Lys 4 methylation in embryos and adult germ cells

AU - Xiao, Y.

AU - Bedet, C.

AU - Robert, V.J.

AU - Simonet, T.

AU - Dunkelbarger, S.

AU - Rakotomalala, C.

AU - Soete, G.

AU - Korswagen, H.C.

AU - Strome, S.

AU - Palladino, F.

N1 - Reporting year: 2011 Metis note: 3100940;

PY - 2011

Y1 - 2011

N2 - Methylation of histone H3 lysine 4 (H3K4me), a mark associated with gene activation, is mediated by SET1 and the related mixed lineage leukemia (MLL) histone methyltransferases (HMTs) across species. Mammals contain seven H3K4 HMTs, Set1A, Set1B, and MLL1-MLL5. The activity of SET1 and MLL proteins relies on protein-protein interactions within large multisubunit complexes that include three core components: RbBP5, Ash2L, and WDR5. It remains unclear how the composition and specificity of these complexes varies between cell types and during development. Caenorhabditis elegans contains one SET1 protein, SET-2, one MLL-like protein, SET-16, and single homologs of RbBP5, Ash2L, and WDR5. Here we show that SET-2 is responsible for the majority of bulk H3K4 methylation at all developmental stages. However, SET-2 and absent, small, or homeotic discs 2 (ASH-2) are differentially required for tri- and dimethylation of H3K4 (H3K4me3 and -me2) in embryos and adult germ cells. In embryos, whereas efficient H3K4me3 requires both SET-2 and ASH-2, H3K4me2 relies mostly on ASH-2. In adult germ cells by contrast, SET-2 serves a major role whereas ASH-2 is dispensable for H3K4me3 and most H3K4me2. Loss of SET-2 results in progressive sterility over several generations, suggesting an important function in the maintenance of a functional germ line. This study demonstrates that individual subunits of SET1-related complexes can show tissue specificity and developmental regulation and establishes C. elegans as a model to study SET1-related complexes in a multicellular organism. [KEYWORDS: Animals, Caenorhabditis elegans/ physiology, Caenorhabditis elegans Proteins/ physiology, Embryo, Nonmammalian/ metabolism, Germ Cells/ metabolism, Histone-Lysine N-Methyltransferase/ physiology, Histones/ metabolism, Lysine/metabolism, Methylation, Nuclear Proteins/ physiology, Saccharomyces cerevisiae Proteins/physiology]

AB - Methylation of histone H3 lysine 4 (H3K4me), a mark associated with gene activation, is mediated by SET1 and the related mixed lineage leukemia (MLL) histone methyltransferases (HMTs) across species. Mammals contain seven H3K4 HMTs, Set1A, Set1B, and MLL1-MLL5. The activity of SET1 and MLL proteins relies on protein-protein interactions within large multisubunit complexes that include three core components: RbBP5, Ash2L, and WDR5. It remains unclear how the composition and specificity of these complexes varies between cell types and during development. Caenorhabditis elegans contains one SET1 protein, SET-2, one MLL-like protein, SET-16, and single homologs of RbBP5, Ash2L, and WDR5. Here we show that SET-2 is responsible for the majority of bulk H3K4 methylation at all developmental stages. However, SET-2 and absent, small, or homeotic discs 2 (ASH-2) are differentially required for tri- and dimethylation of H3K4 (H3K4me3 and -me2) in embryos and adult germ cells. In embryos, whereas efficient H3K4me3 requires both SET-2 and ASH-2, H3K4me2 relies mostly on ASH-2. In adult germ cells by contrast, SET-2 serves a major role whereas ASH-2 is dispensable for H3K4me3 and most H3K4me2. Loss of SET-2 results in progressive sterility over several generations, suggesting an important function in the maintenance of a functional germ line. This study demonstrates that individual subunits of SET1-related complexes can show tissue specificity and developmental regulation and establishes C. elegans as a model to study SET1-related complexes in a multicellular organism. [KEYWORDS: Animals, Caenorhabditis elegans/ physiology, Caenorhabditis elegans Proteins/ physiology, Embryo, Nonmammalian/ metabolism, Germ Cells/ metabolism, Histone-Lysine N-Methyltransferase/ physiology, Histones/ metabolism, Lysine/metabolism, Methylation, Nuclear Proteins/ physiology, Saccharomyces cerevisiae Proteins/physiology]

U2 - 10.1073/pnas.1019290108

DO - 10.1073/pnas.1019290108

M3 - Article

SN - 0027-8424

VL - 108

SP - 8305

EP - 8310

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 20

ER -