title: Association of BMI1 with polycomb bodies is dynamic and requires PRC2/EZH2 and the maintenance DNA methyltransferase DNMT1.
abstract: Polycomb group (PcG) proteins are epigenetic chromatin modifiers involved in heritable gene repression. Two main PcG complexes have been characterized. Polycomb repressive complex 2 (PRC2) is thought to be involved in the initiation of gene silencing, whereas Polycomb repressive complex 1 (PRC1) is implicated in the stable maintenance of gene repression. Here, we investigate the kinetic properties of the binding of one of the PRC1 core components, BMI1, with PcG bodies. PcG bodies are unique nuclear structures located on regions of pericentric heterochromatin, found to be the site of accumulation of PcG complexes in different cell lines. We report the presence of at least two kinetically different pools of BMI1, a highly dynamic and a less dynamic fraction, which may reflect BMI1 pools with different binding capacities to these stable heterochromatin domains. Interestingly, PRC2 members EED and EZH2 appear to be essential for BMI1 recruitment to the PcG bodies. Furthermore, we demonstrate that the maintenance DNA methyltransferase DNMT1 is necessary for proper PcG body assembly independent of DNMT-associated histone deacetylase activity. Together, these results provide new insights in the mechanism for regulation of chromatin silencing by PcG proteins and suggest a highly regulated recruitment of PRC1 to chromatin.
authors.affiliation: Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Hernández-Muñoz
authors.forename: Panthea
authors.initials: P
authors.lastname: Taghavi
authors.forename: Coenraad
authors.initials: C
authors.lastname: Kuijl
authors.forename: Jacques
authors.initials: J
authors.lastname: Neefjes
authors.forename: Maarten
authors.initials: M
authors.lastname: van Lohuizen
mesh_terms: D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D020868:Gene Silencing; D006570:Heterochromatin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism*; D012097:Repressor Proteins / Q000032:analysis / Q000378:metabolism*; D016196:S Phase / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C069077:BMI1 protein, human; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1