期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 435, 期 15, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2023.168162
关键词
gene regulation; hypoxia; hypoxia-inducible factor 1 (HIF-1); ZBTB2; gene subset selection
The cellular response to hypoxia is controlled by a transcription factor called hypoxia-inducible factor 1 (HIF-1). A novel factor, zinc finger and BTB domain-containing protein 2 (ZBTB2), has been found to enhance the expression of certain HIF-1 target genes under hypoxia. ZBTB2 is recruited to the vicinity of hypoxia-responsive element (HREs) on a subset of HIF-1 target gene loci and is required for their full expression under hypoxia.
The cellular response to hypoxia is mainly governed by a transcription factor, hypoxia-inducible factor 1 (HIF-1). Although upregulation of HIF-1 target genes has been hypothesized to require interaction of HIF-1 with other coactivators, much remains to be elucidated regarding the underlying mechanisms. Here, we demonstrate that zinc finger and BTB domain-containing protein 2 (ZBTB2) enhances the expression of certain HIF-1 target genes under hypoxia. ChIP-Seq analysis showed that there is a subset of HIF-1 target genes with overlapping HIF-1 and ZBTB2 peaks. Examination of a representative gene, EGFR anti-sense RNA 1 (EGFR-AS1), showed that HIF-1 binding to the consensus hypoxia-responsive element (HRE) sequence resulted in the recruitment of ZBTB2 to the gene locus and increased p300-mediated histone acetylation, leading to enhanced gene expression under hypoxia. In contrast, expression of HIF-1 target genes lacking ZBTB2 peaks, such as carbonic anhydrase 9 (CA9), was not upregulated by ZBTB2. These findings demonstrate that ZBTB2 is a novel factor that can be recruited to the vicinity of HREs on a subset of HIF-1 target gene loci, and is required for their full expression under hypoxia.& COPY; 2023 Elsevier Ltd. All rights reserved.
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