Ataxin-3 Represses Transcription via Chromatin Binding, Interaction with Histone Deacetylase 3, and Histone Deacetylation

• DOI: 10.1523/jneurosci.2053-06.2006
• Publication Date: 2006-11-02T18:08:27Z
• Authors: Bernd O. Evert; Julieta Araujo; Ana M. Vieira-Sae...; Rob A. I. de Vos; Sigrid Harendza; Thomas Klockgether; Ullrich Wüllner
• Keywords: Histone acetyltransferase; Histone deacetylase 2; SAP30; Corepressor; HDAC4; Histone deacetylase 5; HDAC11

Ataxin-3 (AT3), the disease protein in spinocerebellar ataxia type 3 (SCA3), has been associated with ubiquitin–proteasome system and transcriptional regulation. Here we report that normal AT3 binds to target DNA sequences specific chromatin regions of matrix metalloproteinase-2 (MMP-2) gene promoter represses transcription by recruitment histone deacetylase (HDAC3), nuclear receptor corepressor (NCoR), deacetylation histones bound promoter. Both expanded physiologically interacted HDAC3 NCoR a SCA3 cell model human pons tissue; however, AT3-containing complexes showed increased activity, whereas had reduced activity. Consistently, analyses revealed an acetylation total H3 AT3-expressing cells pons. Expanded lost repressor function displayed altered DNA/chromatin binding was not HDAC3, NCoR, promoter, allowing aberrant MMP-2 via factor GATA-2. For repression cooperates requires its intact ubiquitin-interacting motifs (UIMs), activation is independent UIMs but catalytic cysteine ubiquitin protease domain. These findings demonstrate GATA-2-dependent formation histone-deacetylating requiring UIM-associated function. aberrantly activates site loses ability form deacetylating on regions.