title: Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation.
abstract: How the transcription repressing complex Polycomb interacts with transcriptional regulators at housekeeping genes in somatic cells is not well understood. By exploiting a CpG island (CGI) point mutation causing a Mendelian disease, we show that DNA binding of activating transcription factor (TF) determines histone acetylation and nucleosomal depletion commensurate with Polycomb exclusion from the target promoter. Lack of TF binding leads to reversible transcriptional repression imposed by nucleosomal compaction and consolidated by Polycomb recruitment and establishment of bivalent chromatin status. Thus, within a functional hierarchy of transcriptional regulators, TF binding is the main determinant of Polycomb recruitment to the CGI of a housekeeping gene in somatic cells.
authors.affiliation: Centre for Haematology, Department of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Valentina S
authors.initials: VS
authors.lastname: Caputo
authors.forename: Joana R
authors.initials: JR
authors.lastname: Costa
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Makarona
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Georgiou
authors.forename: D Mark
authors.initials: DM
authors.lastname: Layton
authors.forename: Irene
authors.initials: I
authors.lastname: Roberts
authors.forename: Anastasios
authors.initials: A
authors.lastname: Karadimitris
mesh_terms: D051696:Activating Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000737:chemistry* / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020043:Genes, Essential; D017261:Glycosylphosphatidylinositols / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008364:Mannosyltransferases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism; D017354:Point Mutation; D063146:Polycomb-Group Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012640:Seizures
chemical_list: D051696:Activating Transcription Factors; D004268:DNA-Binding Proteins; D017261:Glycosylphosphatidylinositols; D006657:Histones; D009707:Nucleosomes; D063146:Polycomb-Group Proteins; D008364:Mannosyltransferases; C486036:PIGM protein, human