dc.contributor.author | Nurminen, Veijo | |
dc.contributor.author | Neme, Antonio | |
dc.contributor.author | Seuter, Sabine | |
dc.contributor.author | Carlberg, Carsten | |
dc.date.accessioned | 2019-01-24T08:27:56Z | |
dc.date.available | 2019-01-24T08:27:56Z | |
dc.date.issued | 2019 | |
dc.identifier.uri | https://erepo.uef.fi/handle/123456789/7381 | |
dc.description.abstract | The myeloid master regulator CCAAT enhancer-binding protein alpha (CEBPA) is known as a pioneer factor. In this study, we report the CEBPA cistrome of THP-1 human monocytes after stimulation with the vitamin D receptor (VDR) ligand 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) for 2, 8 and 24 h. About a third of the genomic VDR binding sites co-located with those of CEBPA. In parallel, the binding strength of 5% of the CEBPA cistrome, i.e. some 1500 sites, is significantly (p < 0.001) affected by 1,25(OH)2D3. Transcriptome-wide analysis after CEBPA silencing indicated that the pioneer factor enhances both the basal expression and ligand inducibility of 70 vitamin D target genes largely involved in lipid signaling and metabolism. In contrast, CEBPA suppresses 82 vitamin D target genes many of which are related to the modulation of T cell activity by monocytes. The inducibility of the promoter-specific histone marker H3K4me3 distinguishes the former class of genes from the latter. Moreover, prominent occupancy of the myeloid pioneer factor PU.1 on 1,25(OH)2D3-sensitive CEBPA enhancers mechanistically explains the dichotomy of vitamin D target genes. In conclusion, CEBPA supports vitamin D signaling concerning actions of the innate immune system, but uses the antagonism with PU.1 for suppressing possible overreactions of adaptive immunity. | |
dc.language.iso | englanti | |
dc.publisher | Elsevier BV | |
dc.relation.ispartofseries | BIOCHIMICA ET BIOPHYSICA ACTA - GENE REGULATORY MECHANISMS | |
dc.relation.uri | http://dx.doi.org/10.1016/j.bbagrm.2018.12.004 | |
dc.rights | CC BY-NC-ND 4.0 | |
dc.title | Modulation of vitamin D signaling by the pioneer factor CEBPA | |
dc.description.version | final draft | |
dc.contributor.department | School of Medicine / Biomedicine | |
uef.solecris.id | 59194559 | en |
dc.type.publication | Tieteelliset aikakauslehtiartikkelit | |
dc.relation.doi | 10.1016/j.bbagrm.2018.12.004 | |
dc.description.reviewstatus | peerReviewed | |
dc.format.pagerange | 96-106 | |
dc.publisher.country | Alankomaat | |
dc.relation.issn | 1874-9399 | |
dc.relation.issue | 1 | |
dc.relation.volume | 1862 | |
dc.rights.accesslevel | openAccess | |
dc.type.okm | A1 | |
uef.solecris.openaccess | Ei | |
dc.rights.copyright | © Elsevier B.V. | |
dc.type.displayType | article | en |
dc.type.displayType | artikkeli | fi |
dc.rights.url | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |