Drosophila atrophin homolog functions as a transcriptional corepressor in multiple developmental processes.

Abstract:

:Dentatorubral-pallidoluysian atrophy is a progressive neurodegenerative disease caused by the expansion of a polyglutamine repeats within the Atrophin-1 protein. The in vivo function of Atrophin-1 is unknown. We have characterized a Drosophila gene encoding an Atrophin family protein. Analysis of mutant phenotypes indicates that Drosophila Atrophin is required in diverse developmental processes including early embryonic patterning. Drosophila Atrophin genetically interacts with the transcription repressor even-skipped and is required for its repressive function in vivo. Drosophila Atrophin directly binds to Even-skipped in vitro. Furthermore, both human Atrophin-1 and Drosophila Atrophin repress transcription in vivo when tethered to DNA, and poly-Q expansion in Atrophin-1 reduces this repressive activity. We propose that Atrophin proteins function as versatile transcriptional corepressors and discuss a model that deregulation of transcription may contribute to the pathogenesis of neurodegeneration.

journal_name

Cell

journal_title

Cell

authors

Zhang S,Xu L,Lee J,Xu T

doi

10.1016/s0092-8674(01)00630-4

subject

Has Abstract

pub_date

2002-01-11 00:00:00

pages

45-56

issue

1

eissn

0092-8674

issn

1097-4172

pii

S0092867401006304

journal_volume

108

pub_type

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