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PMID:16618927

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Citation

Terranova, R, Agherbi, H, Boned, A, Meresse, S and Djabali, M (2006) Histone and DNA methylation defects at Hox genes in mice expressing a SET domain-truncated form of Mll. Proc. Natl. Acad. Sci. U.S.A. 103:6629-34

Abstract

The Mll gene is a member of the mammalian trithorax group, involved with the antagonistic Polycomb group in epigenetic regulation of homeotic genes. MLL contains a highly conserved SET domain also found in various chromatin proteins. In this study, we report that mice in which this domain was deleted by homologous recombination in ES cells (DeltaSET) exhibit skeletal defects and altered transcription of particular Hox genes during development. Chromatin immunoprecipitation and bisulfite sequencing analysis on developing embryo tissues demonstrate that this change in gene expression is associated with a dramatic reduction in histone H3 Lysine 4 monomethylation and DNA methylation defects at the same Hox loci. These results establish in vivo that the major function of Mll is to act at the chromatin level to sustain the expression of selected target Hox genes during embryonic development. These observations provide previously undescribed evidence for the in vivo relationship and SET domain dependence between histone methylation and DNA methylation on MLL target genes during embryonic development.

Links

PubMed PMC1440589 Online version:10.1073/pnas.0507425103

Keywords

Animals; Bone and Bones/abnormalities; Bone and Bones/embryology; Cells, Cultured; DNA Methylation; Gene Expression Regulation, Developmental; Genes, Homeobox; Histones/metabolism; Mice; Mice, Knockout; Mice, Mutant Strains; Myeloid-Lymphoid Leukemia Protein/chemistry; Myeloid-Lymphoid Leukemia Protein/genetics; Myeloid-Lymphoid Leukemia Protein/metabolism; Protein Structure, Tertiary; Sequence Deletion

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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