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Postmitotic differentiation of human monocytes requires cohesin-structured chromatin

dc.contributor.authorMinderjahn, Julia
dc.contributor.authorFischer, Alexander
dc.contributor.authorMaier, Konstantin
dc.contributor.authorMendes, Karina
dc.contributor.authorNuetzel, Margit
dc.contributor.authorRaithel, Johanna
dc.contributor.authorStanewsky, Hanna
dc.contributor.authorAckermann, Ute
dc.contributor.authorMånsson, Robert
dc.contributor.authorGebhard, Claudia
dc.contributor.authorRehli, Michael
dc.date.accessioned2022-08-02T12:47:29Z
dc.date.available2022-08-02T12:47:29Z
dc.date.issued2022-12
dc.description.abstractCohesin is a major structural component of mammalian genomes and is required to maintain loop structures. While acute depletion in short-term culture models suggests a limited importance of cohesin for steady-state transcriptional circuits, long-term studies are hampered by essential functions of cohesin during replication. Here, we study genome architecture in a postmitotic differentiation setting, the differentiation of human blood monocytes (MO). We profile and compare epigenetic, transcriptome and 3D conformation landscapes during MO differentiation (either into dendritic cells or macrophages) across the genome and detect numerous architectural changes, ranging from higher level compartments down to chromatin loops. Changes in loop structures correlate with cohesin-binding, as well as epigenetic and transcriptional changes during differentiation. Functional studies show that the siRNA-mediated depletion of cohesin (and to a lesser extent also CTCF) markedly disturbs loop structures and dysregulates genes and enhancers that are primarily regulated during normal MO differentiation. In addition, gene activation programs in cohesin-depleted MO-derived macrophages are disturbed. Our findings implicate an essential function of cohesin in controlling long-term, differentiation- and activation-associated gene expression programs.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1038/s41467-022-31892-2pt_PT
dc.identifier.eid85134725003
dc.identifier.issn2041-1723
dc.identifier.pmcPMC9314343
dc.identifier.pmid35879286
dc.identifier.urihttp://hdl.handle.net/10400.14/38467
dc.identifier.wos001029773300001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titlePostmitotic differentiation of human monocytes requires cohesin-structured chromatinpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue1pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume13pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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