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Nucleic Acids Research Advance Access published online on January 27, 2010

Nucleic Acids Research, doi:10.1093/nar/gkq006

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Involvement of histone deacetylation in MORC2-mediated down-regulation of carbonic anhydrase IX
Shao, Yangguang
Li, Yan
Zhang, Jian
Liu, Di
Liu, Furong
Zhao, Yue
Shen, Tao
Li, Feng
10.1093/nar/gkq006
Nucleic Acids Research 2010, 2010:gkq006v1
2010-01-27
Nucleic Acids Research
2010-01-27

Gene Regulation, Chromatin and Epigenetics
gkq006v1

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© The Author(s) 2010. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Involvement of histone deacetylation in MORC2-mediated down-regulation of carbonic anhydrase IX

Yangguang Shao,
Yan Li,
Jian Zhang,
Di Liu,
Furong Liu,
Yue Zhao,
Tao Shen and
Feng Li^*

Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China

*To whom correspondence should be addressed. Tel: +86 24 23256666/5348; Fax: +86 24 23261056; Email: fli{at}mail.cmu.edu.cn, lifengphd15{at}hotmail.com

Received September 15, 2009. Revised December 20, 2009. Accepted January 5, 2010.

Carbonic anhydrase IX (CAIX) plays an important role in the^{growth and survival of tumor cells. MORC2 is a member of theMORC protein family. The MORC proteins contain a CW-type zincfinger domain and are predicted to have the function of regulatingtranscription, but no MORC2 target genes have been identified.Here we performed a DNA microarray hybridization and found CAIXmRNA to be down-regulated 8-fold when MORC2 was overexpressed.This result was further confirmed by northern and western blotanalysis. Our results also showed that the protected region4 (PR4) was important for the repression function of MORC2.Moreover, MORC2 decreased the acetylation level of histone H3at the CAIX promoter. Meanwhile, trichostatin A (TSA) had anincreasing effect on CAIX promoter activity. Among the six HDACstested, histone deacetylase 4 (HDAC4) had a much more prominenteffect on CAIX repression. ChIP and ChIP Re-IP assays showedthat MORC2 and HDAC4 were assembled on the same region of theCAIX promoter. Importantly, we further confirmed that both proteinsare simultaneously present in the PR4-binding complex. Theseresults may contribute to understanding the molecular mechanismsof CAIX regulation.}

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The authors wish it to be known that, in their opinion, thefirst two authors should be regarded as joint First Authors.

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