ETS transcription factor family member GABPA contributes to vitamin D receptor target gene regulation

被引:21
|
作者
Seuter, Sabine [1 ]
Neme, Antonio [1 ]
Carlberg, Carsten [1 ]
机构
[1] Univ Eastern Finland, Inst Biomed, Sch Med, POB 1627, FI-70211 Kuopio, Finland
来源
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2018年 / 177卷
基金
芬兰科学院;
关键词
Vitamin D; VDR; ETS-domain factor; Monocytes; Epigenomics; ChIP-seq; 1-ALPHA; 25-DIHYDROXYVITAMIN D-3; HUMAN MONOCYTES; RETINOIC ACID; EXPRESSION; PROTEIN; ALPHA; ELEMENTS; HORMONE; SITES;
D O I
10.1016/j.jsbmb.2017.08.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Binding motifs of the ETS-domain transcription factor GABPA are found with high significance below the summits of the vitamin D receptor (VDR) cistrome. VDR is the nuclear receptor for the biologically most active vitamin D metabolite 1 alpha,25-dihydroxyvitamin D-3 (1,25(DE)(2)D-3). In this study, we determined the GABPA cistrome in THP-1 human monocytes and found that it is comprised of 3822 genomic loci, some 20% of which were modulated by 1,25(OH)(2)D-3. The GABPA cistrome showed a high overlap rate with accessible chromatin and the pioneer transcription factor PU.1. Interestingly, 23 and 12% of persistent and transient VDR binding sites, respectively, co-localized with GABPA, which is clearly higher than the rate of secondary VDR loci (4%). Some 40% of GABPA binding sites were found at transcription start sites, nearly 100 of which are of 1,25(OH)(2)D-3 target genes. On 593 genomic loci VDR and GABPA co-localized with PU.1, while only 175 VDR sites bound GABPA in the absence of PU.1. In total, VDR sites with GABPA co-localization may control some 450 vitamin D target genes. Those genes that are co-controlled by PU.1 preferentially participate in cellular and immune signaling processes, while the remaining genes are involved in cellular metabolism pathways. In conclusion, GABPA may contribute to differential VDR target gene regulation.
引用
收藏
页码:46 / 52
页数:7
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