{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Manzo SG"],"funding":["Oncode Institute is partly supported by KWF Dutch Cancer Society","European Research Council","AIRC-Marie Curie iCARE2.0","AIRC-Marie Curie iCARE2.0 (COFUND)","NWO-VICI","EMBO long-term fellowship","Next generation EU-MUR MSCA Young Researcher","EC | FP7 | People | FP7 People: Marie-Curie Actions","EC | FP7 | People | FP7 People: Marie-Curie Actions (FP7 People)"],"pagination":["5260-5287"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11535540"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["43(21)"],"pubmed_abstract":["Lamina-associated domains (LADs) are large chromatin regions that are associated with the nuclear lamina (NL) and form a repressive environment for transcription. The molecular players that mediate gene repression in LADs are currently unknown. Here, we performed FACS-based whole-genome genetic screens in human cells using LAD-integrated fluorescent reporters to identify such regulators. Surprisingly, the screen identified very few NL proteins, but revealed roles for dozens of known chromatin regulators. Among these are the negative elongation factor (NELF) complex and interacting factors involved in RNA polymerase pausing, suggesting that regulation of transcription elongation is a mechanism to repress transcription in LADs. Furthermore, the chromatin remodeler complex BAF and the activation complex Mediator can work both as activators and repressors in LADs, depending on the local context and possibly by rewiring heterochromatin. Our data indicate that the fundamental regulators of transcription and chromatin remodeling, rather than interaction with NL proteins, play a major role in transcription regulation within LADs."],"journal":["The EMBO journal"],"pubmed_title":["Chromatin protein complexes involved in gene repression in lamina-associated domains."],"pmcid":["PMC11535540"],"funding_grant_id":["838555","694466","VI.C.202.098","772471","800924","PNRR_MSCA22SMANZ_01","ALTF158-2018"],"pubmed_authors":["Manzo SG","Brummelkamp TR","Neyazi N","van Ruiten MS","Rowland BD","van Schaik T","Mazouzi A","Leemans C","van Steensel B"],"additional_accession":[]},"is_claimable":false,"name":"Chromatin protein complexes involved in gene repression in lamina-associated domains.","description":"Lamina-associated domains (LADs) are large chromatin regions that are associated with the nuclear lamina (NL) and form a repressive environment for transcription. The molecular players that mediate gene repression in LADs are currently unknown. Here, we performed FACS-based whole-genome genetic screens in human cells using LAD-integrated fluorescent reporters to identify such regulators. Surprisingly, the screen identified very few NL proteins, but revealed roles for dozens of known chromatin regulators. Among these are the negative elongation factor (NELF) complex and interacting factors involved in RNA polymerase pausing, suggesting that regulation of transcription elongation is a mechanism to repress transcription in LADs. Furthermore, the chromatin remodeler complex BAF and the activation complex Mediator can work both as activators and repressors in LADs, depending on the local context and possibly by rewiring heterochromatin. Our data indicate that the fundamental regulators of transcription and chromatin remodeling, rather than interaction with NL proteins, play a major role in transcription regulation within LADs.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-06-03T00:22:29.925Z","creation":"2025-04-04T23:31:49.088Z"},"accession":"S-EPMC11535540","cross_references":{"pubmed":["39322756"],"doi":["10.1038/s44318-024-00214-1"]}}