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Histone H3K4 methylation-dependent and -independent functions of Set1A/COMPASS in embryonic stem cell self-renewal and differentiation.
Sze, Christie C; Cao, Kaixiang; Collings, Clayton K; Marshall, Stacy A; Rendleman, Emily J; Ozark, Patrick A; Chen, Fei Xavier; Morgan, Marc A; Wang, Lu; Shilatifard, Ali.
Afiliação
  • Sze CC; Department of Biochemistry and Molecular Genetics, Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
  • Cao K; Department of Biochemistry and Molecular Genetics, Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
  • Collings CK; Department of Biochemistry and Molecular Genetics, Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
  • Marshall SA; Department of Biochemistry and Molecular Genetics, Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
  • Rendleman EJ; Department of Biochemistry and Molecular Genetics, Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
  • Ozark PA; Department of Biochemistry and Molecular Genetics, Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
  • Chen FX; Department of Biochemistry and Molecular Genetics, Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
  • Morgan MA; Department of Biochemistry and Molecular Genetics, Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
  • Wang L; Department of Biochemistry and Molecular Genetics, Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
  • Shilatifard A; Department of Biochemistry and Molecular Genetics, Robert H. Lurie National Cancer Institute Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Genes Dev ; 31(17): 1732-1737, 2017 09 01.
Article em En | MEDLINE | ID: mdl-28939616
ABSTRACT
Of the six members of the COMPASS (complex of proteins associated with Set1) family of histone H3 Lys4 (H3K4) methyltransferases identified in mammals, Set1A has been shown to be essential for early embryonic development and the maintenance of embryonic stem cell (ESC) self-renewal. Like its familial relatives, Set1A possesses a catalytic SET domain responsible for histone H3K4 methylation. Whether H3K4 methylation by Set1A/COMPASS is required for ESC maintenance and during differentiation has not yet been addressed. Here, we generated ESCs harboring the deletion of the SET domain of Set1A (Set1AΔSET); surprisingly, the Set1A SET domain is dispensable for ESC proliferation and self-renewal. The removal of the Set1A SET domain does not diminish bulk H3K4 methylation in ESCs; instead, only a subset of genomic loci exhibited reduction in H3K4me3 in Set1AΔSET cells, suggesting a role for Set1A independent of its catalytic domain in ESC self-renewal. However, Set1AΔSET ESCs are unable to undergo normal differentiation, indicating the importance of Set1A-dependent H3K4 methylation during differentiation. Our data also indicate that during differentiation, Set1A but not Mll2 functions as the H3K4 methylase on bivalent genes and is required for their expression, supporting a model for transcriptional switch between Mll2 and Set1A during the self-renewing-to-differentiation transition. Together, our study implicates a critical role for Set1A catalytic methyltransferase activity in regulating ESC differentiation but not self-renewal and suggests the existence of context-specific H3K4 methylation that regulates transcriptional outputs during ESC pluripotency.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Histonas / Diferenciação Celular / Histona-Lisina N-Metiltransferase / Células-Tronco Embrionárias Limite: Animals Idioma: En Revista: Genes Dev Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Histonas / Diferenciação Celular / Histona-Lisina N-Metiltransferase / Células-Tronco Embrionárias Limite: Animals Idioma: En Revista: Genes Dev Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos