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http://purl.uniprot.org/citations/21437264http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21437264http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21437264http://www.w3.org/2000/01/rdf-schema#comment"MBT domain proteins are involved in developmental processes and tumorigenesis. In vitro binding and mutagenesis studies have shown that individual MBT domains within clustered MBT repeat regions bind mono- and dimethylated histone lysine residues with little to no sequence specificity but discriminate against the tri- and unmethylated states. However, the exact function of promiscuous histone methyl-lysine binding in the biology of MBT domain proteins has not been elucidated. Here, we show that the Caenorhabditis elegans four MBT domain protein LIN-61, in contrast to other MBT repeat factors, specifically interacts with histone H3 when methylated on lysine 9, displaying a strong preference for di- and trimethylated states (H3K9me2/3). Although the fourth MBT repeat is implicated in this interaction, H3K9me2/3 binding minimally requires MBT repeats two to four. Further, mutagenesis of residues conserved with other methyl-lysine binding MBT regions in the fourth MBT repeat does not abolish interaction, implicating a distinct binding mode. In vivo, H3K9me2/3 interaction of LIN-61 is required for C. elegans vulva development within the synMuvB pathway. Mutant LIN-61 proteins deficient in H3K9me2/3 binding fail to rescue lin-61 synMuvB function. Also, previously identified point mutant synMuvB alleles are deficient in H3K9me2/3 interaction although these target residues that are outside of the fourth MBT repeat. Interestingly, lin-61 genetically interacts with two other synMuvB genes, hpl-2, an HP1 homologous H3K9me2/3 binding factor, and met-2, a SETDB1 homologous H3K9 methyl transferase (H3K9MT), in determining C. elegans vulva development and fertility. Besides identifying the first sequence specific and di-/trimethylation binding MBT domain protein, our studies imply complex multi-domain regulation of ligand interaction of MBT domains. Our results also introduce a mechanistic link between LIN-61 function and biology, and they establish interplay of the H3K9me2/3 binding proteins, LIN-61 and HPL-2, as well as the H3K9MT MET-2 in distinct developmental pathways."xsd:string
http://purl.uniprot.org/citations/21437264http://purl.org/dc/terms/identifier"doi:10.1371/journal.pgen.1002017"xsd:string
http://purl.uniprot.org/citations/21437264http://purl.org/dc/terms/identifier"doi:10.1371/journal.pgen.1002017"xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/author"Fischle W."xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/author"Fischle W."xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/author"Koester-Eiserfunke N."xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/author"Koester-Eiserfunke N."xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/name"PLoS Genet."xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/name"PLoS Genet."xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/pages"E1002017"xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/pages"E1002017"xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/title"H3K9me2/3 binding of the MBT domain protein LIN-61 is essential for Caenorhabditis elegans vulva development."xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/title"H3K9me2/3 binding of the MBT domain protein LIN-61 is essential for Caenorhabditis elegans vulva development."xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/21437264http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/21437264http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21437264
http://purl.uniprot.org/citations/21437264http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21437264
http://purl.uniprot.org/citations/21437264http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21437264
http://purl.uniprot.org/citations/21437264http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21437264
http://purl.uniprot.org/uniprot/P34544http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/21437264
http://purl.uniprot.org/uniprot/B2D6M2http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/21437264