Format:
Online-Ressource
ISSN:
1460-2075
Content:
v‐ErbA, a mutated thyroid hormone receptor alpha (TRα), is thought to contribute to avian erythroblastosis virus (AEV)‐induced leukemic transformation by constitutively repressing transcription of target genes. However, the binding of v‐ErbA or any unliganded nuclear receptor to a chromatin‐embedded response element as well as the role of the N‐CoR–SMRT–HDAC co‐repressor complex in mediating repression remain hypothetical. Here we identify a v‐ErbA‐response element, VRE, in an intronic DNase I hypersensitive site (HS2) of the chicken erythroid carbonic anhydrase II (CAII) gene. In vivo footprinting shows that v‐ErbA is constitutively bound to this HS2‐VRE in transformed, undifferentiated erythroblasts along with other transcription factors like GATA‐1. Transfection assays show that the repressed HS2 region can be turned into a potent enhancer in v‐ErbA‐expressing cells by mutation of the VRE. Differentiation of transformed cells alleviates v‐ErbA binding concomitant with activation of CAII transcription. Co‐expression of a gag–TRα fusion protein in AEV‐transformed cells and addition of ligand derepresses CAII transcription. Treatment of transformed cells with the histone deacetylase inhibitor, trichostatin A, derepresses the endogenous, chromatin‐embedded CAII gene, while a transfected HS2‐enhancer construct remains repressed. Taken together, our data suggest that v‐ErbA prevents CAII activation by ‘neutralizing’ in cis the activity of erythroid transcription factors.
In:
volume:17
In:
number:24
In:
year:1998
In:
pages:7382-7394
In:
extent:13
In:
European Molecular Biology Organization, The EMBO journal, Heidelberg : EMBO Press, 1982-, 17, Heft 24 (1998), 7382-7394 (gesamt 13), 1460-2075
Language:
English
DOI:
10.1093/emboj/17.24.7382
URN:
urn:nbn:de:101:1-2024010406053933719372
URL:
https://doi.org/10.1093/emboj/17.24.7382
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2024010406053933719372
URL:
https://d-nb.info/1315020750/34
URL:
https://doi.org/10.1093/emboj/17.24.7382
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