Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation
Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development. However, the mechanisms by which these complexes recognize their target sites and function together to form repressive chromati...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2014
|
| _version_ | 1797062708485423104 |
|---|---|
| author | Blackledge, N Farcas, A Kondo, T King, H McGouran, J Hanssen, L Ito, S Cooper, S Kondo, K Koseki, Y Ishikura, T Long, H Sheahan, T Brockdorff, N Kessler, B Koseki, H Klose, R |
| author_facet | Blackledge, N Farcas, A Kondo, T King, H McGouran, J Hanssen, L Ito, S Cooper, S Kondo, K Koseki, Y Ishikura, T Long, H Sheahan, T Brockdorff, N Kessler, B Koseki, H Klose, R |
| author_sort | Blackledge, N |
| collection | OXFORD |
| description | Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development. However, the mechanisms by which these complexes recognize their target sites and function together to form repressive chromatin domains remain poorly understood. Recruitment of PRC1 to target sites has been proposed to occur through a hierarchical process, dependent on prior nucleation of PRC2 and placement of H3K27me3. Here, using a de novo targeting assay in mouse embryonic stem cells we unexpectedly discover that PRC1-dependent H2AK119ub1 leads to recruitment of PRC2 and H3K27me3 to effectively initiate a polycomb domain. This activity is restricted to variant PRC1 complexes, and genetic ablation experiments reveal that targeting of the variant PCGF1/PRC1 complex by KDM2B to CpG islands is required for normal polycomb domain formation and mouse development. These observations provide a surprising PRC1-dependent logic for PRC2 occupancy at target sites in vivo. |
| first_indexed | 2024-03-06T20:49:26Z |
| format | Journal article |
| id | oxford-uuid:37141780-8ad2-435f-b22a-7a9b1929dd06 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:49:26Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:37141780-8ad2-435f-b22a-7a9b1929dd062022-03-26T13:41:46ZVariant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain FormationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:37141780-8ad2-435f-b22a-7a9b1929dd06EnglishSymplectic Elements at OxfordElsevier2014Blackledge, NFarcas, AKondo, TKing, HMcGouran, JHanssen, LIto, SCooper, SKondo, KKoseki, YIshikura, TLong, HSheahan, TBrockdorff, NKessler, BKoseki, HKlose, RChromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development. However, the mechanisms by which these complexes recognize their target sites and function together to form repressive chromatin domains remain poorly understood. Recruitment of PRC1 to target sites has been proposed to occur through a hierarchical process, dependent on prior nucleation of PRC2 and placement of H3K27me3. Here, using a de novo targeting assay in mouse embryonic stem cells we unexpectedly discover that PRC1-dependent H2AK119ub1 leads to recruitment of PRC2 and H3K27me3 to effectively initiate a polycomb domain. This activity is restricted to variant PRC1 complexes, and genetic ablation experiments reveal that targeting of the variant PCGF1/PRC1 complex by KDM2B to CpG islands is required for normal polycomb domain formation and mouse development. These observations provide a surprising PRC1-dependent logic for PRC2 occupancy at target sites in vivo. |
| spellingShingle | Blackledge, N Farcas, A Kondo, T King, H McGouran, J Hanssen, L Ito, S Cooper, S Kondo, K Koseki, Y Ishikura, T Long, H Sheahan, T Brockdorff, N Kessler, B Koseki, H Klose, R Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation |
| title | Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation |
| title_full | Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation |
| title_fullStr | Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation |
| title_full_unstemmed | Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation |
| title_short | Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation |
| title_sort | variant prc1 complex dependent h2a ubiquitylation drives prc2 recruitment and polycomb domain formation |
| work_keys_str_mv | AT blackledgen variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT farcasa variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT kondot variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT kingh variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT mcgouranj variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT hanssenl variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT itos variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT coopers variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT kondok variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT kosekiy variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT ishikurat variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT longh variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT sheahant variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT brockdorffn variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT kesslerb variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT kosekih variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation AT kloser variantprc1complexdependenth2aubiquitylationdrivesprc2recruitmentandpolycombdomainformation |