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Sci Rep. 2015 Jul 15;5:11979. doi: 10.1038/srep11979.

ZBTB20 is a sequence-specific transcriptional repressor of alpha-fetoprotein gene.

Author information

1
1] Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China [2].
2
Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
3
Department of Microbiology, Immunology &Molecular Genetics, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA.
4
MOE Key Laboratory for Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Abstract

Alpha-fetoprotein (AFP) represents a classical model system to study developmental gene regulation in mammalian cells. We previously reported that liver ZBTB20 is developmentally regulated and plays a central role in AFP postnatal repression. Here we show that ZBTB20 is a sequence-specific transcriptional repressor of AFP. By ELISA-based DNA-protein binding assay and conventional gel shift assay, we successfully identified a ZBTB20-binding site at -104/-86 of mouse AFP gene, flanked by two HNF1 sites and two C/EBP sites in the proximal promoter. Importantly, mutation of the core sequence in this site fully abolished its binding to ZBTB20 in vitro, as well as the repression of AFP promoter activity by ZBTB20. The unique ZBTB20 site was highly conserved in rat and human AFP genes, but absent in albumin genes. These help to explain the autonomous regulation of albumin and AFP genes in the liver after birth. Furthermore, we demonstrated that transcriptional repression of AFP gene by ZBTB20 was liver-specific. ZBTB20 was dispensable for AFP silencing in other tissues outside liver. Our data define a cognate ZBTB20 site in AFP promoter which mediates the postnatal repression of AFP gene in the liver.

PMID:
26173901
PMCID:
PMC4648434
DOI:
10.1038/srep11979
[Indexed for MEDLINE]
Free PMC Article

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