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

abstract

  • 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 TC-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 TC-6 cells, but not in human islet cells; (ii) down-regulation of ZBED6 in TC-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.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 3

author list (cited authors)

  • Wang, X., Jiang, L., Wallerman, O., Engstrm, U., Ameur, A., Gupta, R. K., ... Welsh, N.

citation count

  • 16

complete list of authors

  • Wang, Xuan||Jiang, Lin||Wallerman, Ola||Engström, Ulla||Ameur, Adam||Gupta, Rajesh Kumar||Qi, Yu||Andersson, Leif||Welsh, Nils

publication date

  • October 2013