The v-ErbA oncoprotein quenches the activity of an erythroid-specific enhancer

Oncogene
G G BraliouH Stunnenberg

Abstract

v-ErbA is a mutated variant of thyroid hormone receptor (TRalpha/NR1A1) borne by the Avian Erythroblastosis virus causing erythroleukemia. TRalpha is known to activate transcription of specific genes in the presence of its cognate ligand, T3 hormone, while in its absence it represses it. v-ErbA is unable to bind ligand, and hence is thought to contribute to leukemogenesis by actively repressing erythroid-specific genes such as the carbonic anhydrase II gene (CA II). In the prevailing model, v-ErbA occludes liganded TR from binding to its cognate elements and constitutively interacts with the corepressors NCoR/SMRT. We previously identified a v-ErbA responsive element (VRE) within a DNase I hypersensitive region (HS2) located in the second intron of the CA II gene. We now show that HS2 fulfils all the requirements for a genuine enhancer that functions independent of its orientation and position with a profound erythroid-specific activity in normal erythroid progenitors (T2ECs) and in leukemic erythroid cell lines. We find that the HS2 enhancer activity is governed by two adjacent GATA-factor binding sites. v-ErbA as well as unliganded TR prevent HS2 activity by nullifying the positive function of factors bound to GATA-sites. How...Continue Reading

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Citations

Mar 13, 2002·The EMBO Journal·Luc E G RietveldHendrik G Stunnenberg
Oct 27, 2007·BMC Genomics·Corinne BressonSandrine Gonin-Giraud
Jan 20, 2004·The Journal of Biological Chemistry·Laura J DeLongLizabeth A Allison
Jun 23, 2001·Oncogene·L E RietveldH G Stunnenberg
Jan 15, 2005·Molecular Endocrinology·Ghislain M C BonamyLizabeth A Allison

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