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

Citations Over TimeTop 10% of 2015 papers

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.

Related Papers

• → The three operators of the lac operon cooperate in repression.(1990)491 cited
• → Non-canonical Staphylococcus aureus pathogenicity island repression(2022)10 cited
• → Protein-protein interaction between the transcriptional repressor E4BP4 and the TBP-binding protein Dr1(1996)39 cited
• → Functional similarity of Knirps CtBP-dependent and CtBP-independent transcriptional repressor activities(2003)33 cited
• → Analysis of URSG-mediated glucose repression of the GAL1 promoter of Saccharomyces cerevisiae.(1992)48 cited