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Modulation of vitamin D signaling by the pioneer factor CEBPA

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Date
2019
Author(s)
Nurminen, Veijo
Neme, Antonio
Seuter, Sabine
Carlberg, Carsten
Unique identifier
10.1016/j.bbagrm.2018.12.004
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Citation
Nurminen, Veijo. Neme, Antonio. Seuter, Sabine. Carlberg, Carsten. (2019). Modulation of vitamin D signaling by the pioneer factor CEBPA.  BIOCHIMICA ET BIOPHYSICA ACTA - GENE REGULATORY MECHANISMS, 1862 (1) , 96-106. 10.1016/j.bbagrm.2018.12.004.
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© Elsevier B.V.
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CC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
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.

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https://erepo.uef.fi/handle/123456789/7381
Link to the original item
http://dx.doi.org/10.1016/j.bbagrm.2018.12.004
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Elsevier BV
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  • Terveystieteiden tiedekunta [1335]
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