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Endothelial cell differentiation is encompassed by changes in long range interactions between inactive chromatin regions

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cris.lastimport.scopus2024-02-12T19:57:22Z
dc.abstract.enEndothelial cells (ECs) differentiate from mesodermal progenitors during vasculogenesis. By comparing changes in chromatin interactions between human umbilical vein ECs, embryonic stem cells and mesendoderm cells, we identified regions exhibiting EC-specific compartmentalization and changes in the degree of connectivity within topologically associated domains (TADs). These regions were characterized by EC-specific transcription, binding of lineage-determining transcription factors and cohesin. In addition, we identified 1200 EC-specific long-range interactions (LRIs) between TADs. Most of the LRIs were connected between regions enriched for H3K9me3 involving pericentromeric regions, suggesting their involvement in establishing compartmentalization of heterochromatin during differentiation. Second, we provide evidence that EC-specific LRIs correlate with changes in the hierarchy of chromatin aggregation. Despite these rearrangements, the majority of chromatin domains fall within a pre-established hierarchy conserved throughout differentiation. Finally, we investigated the effect of hypoxia on chromatin organization. Although hypoxia altered the expression of hundreds of genes, minimal effect on chromatin organization was seen. Nevertheless, 70% of hypoxia-inducible genes situated within a TAD bound by HIF1α suggesting that transcriptional responses to hypoxia largely depend on pre-existing chromatin organization. Collectively our results show that large structural rearrangements establish chromatin architecture required for functional endothelium and this architecture remains largely unchanged in response to hypoxia.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorZaborowski, Rafał
dc.contributor.authorWilczyński, Bartosz
dc.contributor.authorNiskanen, Henri
dc.contributor.authorKaikkonen, Minna U
dc.contributor.authorYlä-Herttuala, Seppo
dc.contributor.authorHeinäniemi, Merja
dc.contributor.authorTuszyńska, Irina
dc.date.accessioned2024-01-24T22:47:38Z
dc.date.available2024-01-24T22:47:38Z
dc.date.issued2018
dc.description.financeNie dotyczy
dc.description.number4
dc.description.volume46
dc.identifier.doi10.1093/NAR/GKX1214
dc.identifier.issn0305-1048
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/106166
dc.identifier.weblinkhttps://academic.oup.com/nar/article/46/4/1724/4690582
dc.languageeng
dc.pbn.affiliationcomputer and information sciences
dc.relation.ispartofNucleic Acids Research
dc.relation.pages1724–1740
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleEndothelial cell differentiation is encompassed by changes in long range interactions between inactive chromatin regions
dc.typeJournalArticle
dspace.entity.typePublication