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PMID: 16481466 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Histone deacetylase-associating Atrophin proteins are nuclear receptor corepressors.

Genes & development ·Vol. 20 ·No. 5 ·2006-03-01 ·Pages 525-30

Wang L, Rajan H, Pitman JL, McKeown M, Tsai CC

Abstract

Drosophila Tailless (Tll) is an orphan nuclear receptor involved in embryonic segmentation and neurogenesis. Although Tll exerts potent transcriptional repressive effects, the underlying molecular mechanisms have not been determined. Using the established regulation of knirps by tll as a paradigm, we report that repression of knirps by Tll involves Atrophin, which is related to vertebrate Atrophin-1 and Atrophin-2. Atrophin interacts with Tll physically and genetically, and both proteins localize to the same knirps promoter region. Because Atrophin proteins interact with additional nuclear receptors and Atrophin-2 selectively binds histone deacetylase 1/2 (HDAC1/2) through its ELM2 (EGL-27 and MTA1 homology 2)/SANT (SWI3/ADA2/N-CoR/TFIII-B) domains, our study establishes that Atrophin proteins represent a novel class of nuclear receptor corepressors.

MeSH Terms
Alanine/metabolism Amino Acid Motifs Amino Acid Sequence Amino Acid Substitution Animals Cell Line Conserved Sequence DNA-Binding Proteins/chemistry,genetics,metabolism Drosophila/embryology,genetics Drosophila Proteins/chemistry,genetics,metabolism Embryo, Nonmammalian Glutathione Transferase/metabolism Histone Deacetylases/genetics,metabolism Humans Models, Biological Molecular Sequence Data Mutation Nuclear Proteins/genetics,metabolism Nuclear Receptor Co-Repressor 1 Promoter Regions, Genetic Protein Structure, Tertiary Recombinant Fusion Proteins/metabolism Repressor Proteins/chemistry,genetics,metabolism Sequence Alignment Sequence Homology, Amino Acid Transcription Factors/chemistry,genetics,metabolism Two-Hybrid System Techniques beta-Galactosidase/analysis,metabolism
Chemicals
DNA-Binding Proteins Drosophila Proteins NCOR1 protein, human Nuclear Proteins Nuclear Receptor Co-Repressor 1 Recombinant Fusion Proteins Repressor Proteins TLL protein, Drosophila Transcription Factors gug protein, Drosophila kni protein, Drosophila Glutathione Transferase beta-Galactosidase Histone Deacetylases Alanine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Wang Lei
Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Rajan Harini
Pitman Jeffrey L
McKeown Michael
Tsai Chih-Cheng
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1393506
Published
2006-03-01
Epub
2006-00-15
Pages
525-30
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1410805
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1393506 PMC Full Text View journal details
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