<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=undefined&type=result"></script>');
-->
</script>

COPY SCRIPT

For further information contact us at helpdesk@openaire.eu

Dysregulation of upstream binding factor-1 acetylation at K352 is linked to impaired ribosomal DNA transcription in Huntington's disease

descriptionPublicationkeyboard_double_arrow_right Article 06 May 2011 English Publisher:Springer Science and Business Media LLCJournal:Cell Death & Differentiation, volume 18, pages 1,726-1,735 (issn: 1350-9047, eissn: 1476-5403,

Authors: Hoon Ryu; Hoon Ryu; Hoon Ryu; Yu Jin Hwang; Dohyun Han; Kristina Todorova; Kristina Todorova; +6 Authors

doi: 10.1038/cdd.2011.38

pmid: 21546905

pmc: PMC3154516

Dysregulation of upstream binding factor-1 acetylation at K352 is linked to impaired ribosomal DNA transcription in Huntington's disease

- Summary
- Subjects
- Related research
  (6)
- Metrics

Abstract

Huntington's disease (HD) is an autosomal-dominant neurological disorder caused by expanded CAG repeats in the Huntingtin (Htt) gene, but it is not known how this mutation causes neurodegeneration. Herein, we found that dysfunction of upstream binding factor-1 (UBF-1) is linked to reduced ribosomal DNA (rDNA) transcription in HD. We identified that UBF1 acetylation at Lys (K) 352 by CREB binding protein (CBP) is crucial for the transcriptional activity of rDNA. UBF1 mutation (K352A, K352Q, and K352R) decreased rDNA transcriptional activity. Moreover, both CBP-dHAT mutant and knockdown of CBP by siRNA reduced acetylation of UBF1 and resulted in the decreased transcription of rDNA into rRNA. ChIP analysis showed a significant reduction of UBF1 occupancy in the promoter of rDNA in STHdh(Q111) cell line model of HD. These results demonstrate that abnormal activity of UBF1 and its acetylation by CBP are linked to impaired rDNA transcription in HD. This novel mechanism suggests that modulation of UBF-mediated rDNA synthesis by CBP may be a therapeutic target for improving neuronal rDNA transcription in HD.

Related Organizations

Seoul National University
Korea (Republic of)
Boston College
United States
Boston University
United States
New Generation University College
Ethiopia
VA Boston Healthcare System
United States

Keywords

Male, Chromatin Immunoprecipitation, Transcription, Genetic, Lysine, Acetylation, Mice, Transgenic, CREB-Binding Protein, DNA, Ribosomal, Cell Line, Disease Models, Animal, Mice, Huntington Disease, Mutation, Animals, RNA Interference, RNA, Small Interfering, Promoter Regions, Genetic, Pol1 Transcription Initiation Complex Proteins

6 Research products, page 1 of 1

Upstream binding transcription factor, RNA polymerase I, isoform CRA_a
2017IsRelatedTo
Nucleolar transcription factor 1
2017IsRelatedTo
Ubtf protein
2017IsRelatedTo
Uncharacterized protein
2017IsRelatedTo
Nucleolar transcription factor 1
2017IsRelatedTo
Nucleolar transcription factor 1
2017IsRelatedTo

Impact byBIP!

	citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).	49
	popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.	Top 10%
	influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).	Top 10%
	impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.	Top 10%