Repository logo
 
Publication

The epigenetic pioneer EGR2 initiates DNA demethylation in differentiating monocytes at both stable and transient binding sites

2021-12Journal article Open access
Simple item page
dc.contributor.authorMendes, Karina
dc.contributor.authorSchmidhofer, Sandra
dc.contributor.authorMinderjahn, Julia
dc.contributor.authorGlatz, Dagmar
dc.contributor.authorKiesewetter, Claudia
dc.contributor.authorRaithel, Johanna
dc.contributor.authorWimmer, Julia
dc.contributor.authorGebhard, Claudia
dc.contributor.authorRehli, Michael
dc.date.accessioned2021-03-29T09:26:17Z
dc.date.available2021-03-29T09:26:17Z
dc.date.issued2021-12
dc.description.abstractThe differentiation of human blood monocytes (MO), the post-mitotic precursors of macrophages (MAC) and dendritic cells (moDC), is accompanied by the active turnover of DNA methylation, but the extent, consequences and mechanisms of DNA methylation changes remain unclear. Here, we profile and compare epigenetic landscapes during IL-4/GM-CSF-driven MO differentiation across the genome and detect several thousand regions that are actively demethylated during culture, both with or without accompanying changes in chromatin accessibility or transcription factor (TF) binding. We further identify TF that are globally associated with DNA demethylation processes. While interferon regulatory factor 4 (IRF4) is found to control hallmark dendritic cell functions with less impact on DNA methylation, early growth response 2 (EGR2) proves essential for MO differentiation as well as DNA methylation turnover at its binding sites. We also show that ERG2 interacts with the 5mC hydroxylase TET2, and its consensus binding sequences show a characteristic DNA methylation footprint at demethylated sites with or without detectable protein binding. Our findings reveal an essential role for EGR2 as epigenetic pioneer in human MO and suggest that active DNA demethylation can be initiated by the TET2-recruiting TF both at stable and transient binding sites.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1038/s41467-021-21661-ypt_PT
dc.identifier.eid85102247894
dc.identifier.issn2041-1723
dc.identifier.pmcPMC7946903
dc.identifier.pmid33692344
dc.identifier.urihttp://hdl.handle.net/10400.14/32342
dc.identifier.wos000627889300007
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleThe epigenetic pioneer EGR2 initiates DNA demethylation in differentiating monocytes at both stable and transient binding sitespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue1pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume12pt_PT
person.familyNameRehli
person.givenNameMichael
person.identifier.orcid0000-0003-3992-932X
person.identifier.scopus-author-id6701654457
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication7dbabab5-a67a-47e0-a3a3-1647d4fa339c
relation.isAuthorOfPublication.latestForDiscovery7dbabab5-a67a-47e0-a3a3-1647d4fa339c

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
28707140.pdf
Size:
4.1 MB
Format:
Adobe Portable Document Format
Download

Collections

CIIS - Contribuições em Revistas Científicas / Contribution to Journals