Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation
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) det...
| Main Authors: | , , , , , , |
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| פורמט: | Journal article |
| שפה: | English |
| יצא לאור: |
Oxford University Press
2013
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| _version_ | 1826311875128721408 |
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| author | Caputo, VS Costa, JR Makarona, K Georgiou, E Layton, DM Roberts, I Karadimitris, A |
| author_facet | Caputo, VS Costa, JR Makarona, K Georgiou, E Layton, DM Roberts, I Karadimitris, A |
| author_sort | Caputo, VS |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T08:17:42Z |
| format | Journal article |
| id | oxford-uuid:c7ddf48e-2e7e-4db5-8681-e152d6e1de2d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:17:42Z |
| publishDate | 2013 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:c7ddf48e-2e7e-4db5-8681-e152d6e1de2d2024-01-09T09:02:36ZMechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c7ddf48e-2e7e-4db5-8681-e152d6e1de2dEnglishSymplectic Elements at OxfordOxford University Press2013Caputo, VSCosta, JRMakarona, KGeorgiou, ELayton, DMRoberts, IKaradimitris, AHow 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. |
| spellingShingle | Caputo, VS Costa, JR Makarona, K Georgiou, E Layton, DM Roberts, I Karadimitris, A Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation |
| title | Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation |
| title_full | Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation |
| title_fullStr | Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation |
| title_full_unstemmed | Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation |
| title_short | Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation |
| title_sort | mechanism of polycomb recruitment to cpg islands revealed by inherited disease associated mutation |
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