Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation.
Τίτλος | Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Caputo, V. S., Costa J. R., Makarona K., Georgiou E., D Layton M., Roberts I., & Karadimitris A. |
Journal | Hum Mol Genet |
Volume | 22 |
Issue | 16 |
Pagination | 3187-94 |
Date Published | 2013 Aug 15 |
ISSN | 1460-2083 |
Λέξεις κλειδιά | Activating Transcription Factors, B-Lymphocytes, Base Sequence, Cells, Cultured, CpG Islands, DNA Methylation, DNA-Binding Proteins, Gene Expression Regulation, Genes, Essential, Glycosylphosphatidylinositols, Hemoglobinuria, Paroxysmal, Histones, Humans, Mannosyltransferases, Molecular Sequence Data, Nucleosomes, Point Mutation, Polycomb-Group Proteins, Promoter Regions, Genetic, Protein Binding, Seizures |
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. |
DOI | 10.1093/hmg/ddt171 |
Alternate Journal | Hum Mol Genet |
PubMed ID | 23591993 |
Grant List | G0802401 / / Medical Research Council / United Kingdom |