PMID- 9857194
OWN - NLM
STAT- MEDLINE
DCOM- 19990216
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 17
IP  - 24
DP  - 1998 Dec 15
TI  - Leukemic transformation by the v-ErbA oncoprotein entails constitutive binding to 
      and repression of an erythroid enhancer in vivo.
PG  - 7382-94
AB  - v-ErbA, a mutated thyroid hormone receptor alpha (TRalpha), 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-TRalpha 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.
FAU - Ciana, P
AU  - Ciana P
AD  - Gene Expression Program, EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
FAU - Braliou, G G
AU  - Braliou GG
FAU - Demay, F G
AU  - Demay FG
FAU - von Lindern, M
AU  - von Lindern M
FAU - Barettino, D
AU  - Barettino D
FAU - Beug, H
AU  - Beug H
FAU - Stunnenberg, H G
AU  - Stunnenberg HG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Oncogene Proteins v-erbA)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 3X2S926L3Z (trichostatin A)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Alpharetrovirus
MH  - Animals
MH  - Base Sequence
MH  - Carbonic Anhydrases/biosynthesis/*genetics
MH  - Cell Differentiation
MH  - *Cell Transformation, Neoplastic
MH  - DNA Footprinting
MH  - Enhancer Elements, Genetic
MH  - Erythropoiesis
MH  - Gene Expression Regulation, Neoplastic
MH  - Histone Deacetylase Inhibitors
MH  - Hydroxamic Acids/pharmacology
MH  - Introns
MH  - Leukemia/*genetics
MH  - Molecular Sequence Data
MH  - Oncogene Proteins v-erbA/*metabolism
MH  - Protein Binding
MH  - Receptors, Thyroid Hormone/metabolism
MH  - *Response Elements
PMC - PMC1171083
EDAT- 1998/12/19 00:00
MHDA- 1998/12/19 00:01
PMCR- 1999/12/15
CRDT- 1998/12/19 00:00
PHST- 1998/12/19 00:00 [pubmed]
PHST- 1998/12/19 00:01 [medline]
PHST- 1998/12/19 00:00 [entrez]
PHST- 1999/12/15 00:00 [pmc-release]
AID - 10.1093/emboj/17.24.7382 [doi]
PST - ppublish
SO  - EMBO J. 1998 Dec 15;17(24):7382-94. doi: 10.1093/emboj/17.24.7382.