Transcription factor ZBED6 affects gene expression, proliferation, and cell death in pancreatic beta cells.

Wang X, Jiang L, Wallerman O, Engström U, Ameur A, Gupta RK, Qi Y, Andersson L, Welsh N

Proc. Natl. Acad. Sci. U.S.A. 110 (40) 15997-16002 [2013-10-01; online 2013-09-18]

We have investigated whether the recently discovered transcription factor, zinc finger BED domain-containing protein 6 (ZBED6), is expressed in insulin-producing cells and, if so, to what extent it affects beta cell function. ZBED6 was translated from a ZC3H11A transcript in which the ZBED6-containing intron was retained. ZBED6 was present in mouse βTC-6 cells and human islets as a double nuclear band at 115/120 kDa and as a single cytoplasmic band at 95-100 kDa, which lacked N-terminal nuclear localization signals. We propose that ZBED6 supports proliferation and survival of beta cells, possibly at the expense of specialized beta cell function-i.e., insulin production-because (i) the nuclear ZBED6 were the predominant forms in rapidly proliferating βTC-6 cells, but not in human islet cells; (ii) down-regulation of ZBED6 in βTC-6 cells resulted in altered morphology, decreased proliferation, a partial S/G2 cell-cycle arrest, increased expression of beta cell-specific genes, and higher rates of apoptosis; (iii) silencing of ZBED6 in the human PANC-1 duct cell line reduced proliferation rates; and (iv) ZBED6 binding was preferentially to genes that control transcription, macromolecule biosynthesis, and apoptosis. Furthermore, it is possible that beta cells, by switching from full length to a truncated form of ZBED6, can decide the subcellular localization of ZBED6, thereby achieving differential ZBED6-mediated transcriptional regulation.

NGI Uppsala (SNP&SEQ Technology Platform)

NGI Uppsala (Uppsala Genome Center)

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PubMed 24043816

DOI 10.1073/pnas.1303625110

Crossref 10.1073/pnas.1303625110

1303625110

pmc PMC3791784