Abstract
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease that results from a pathogenic glutamine-repeat expansion in the protein ataxin-1 (ATXN1). Although the functions of ATXN1 are still largely unknown, there is evidence to suggest that ATXN1 plays a role in regulating gene expression, the earliest process known to go awry in SCA1 mouse models. In this study, we show that ATXN1 reduces histone acetylation, a post-translational modification of histones associated with enhanced transcription, and represses histone acetyl transferase-mediated transcription. In addition, we find that depleting the Leucine-rich Acidic Nuclear Protein (LANP)-an ATXN1 binding inhibitor of histone acetylation-reverses aspects of SCA1 neuritic pathology.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 526-532 |
| Number of pages | 7 |
| Journal | Neurobiology of Disease |
| Volume | 48 |
| Issue number | 3 |
| DOIs | |
| State | Published - Dec 2012 |
Bibliographical note
Funding Information:We thank members of the Opal lab for their intellectual input. P.O. wishes to thank Huda Zoghbi for discussions in the early stages of this project. This work was funded by the U.S. National Institutes of Health grants K02 NS051340 ; R21 NS060080 , and R01 NS062051 ; with additional funding from the National Organization for Rare Disorders , the National Ataxia Foundation , and the Brain Research Foundation (P.O.). M.C. and R.K. received funding from the U.S. National Institutes of Health training grant T32 .
Keywords
- ANP32-A
- LANP
- Neurite outgrowth
- Pp32
- SCA1
- Spinocerebellar ataxia type 1
