Skip Navigation



Human Molecular Genetics Advance Access published online on March 4, 2008
Human Molecular Genetics, doi:10.1093/hmg/ddn067
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
17/12/1774    most recent
ddn067v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Lee, J.
Right arrow Articles by Ryu, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, J.
Right arrow Articles by Ryu, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Monoallele Deletion of CBP Leads to Pericentromeric Heterochromatin Condensation through ESET Expression and Histone H3 (K9) Methylation

Junghee Lee1,4, Sean Hagerty1,4, Kerry A. Cormier1,4, Robert J. Ferrante1,2,3,4, Andrew L. Kung5 and Hoon Ryu1,4,*

1 Department of Neurology, Clinical Center, Bedford Veteran's Affairs Medical Center, Bedford, MA 01730 2 Pathology, Clinical Center, Bedford Veteran's Affairs Medical Center, Bedford, MA 01730 3 Psychiatry Departments, Boston University School of Medicine, Boston, MA 02118 4 Geriatric Research Education and Clinical Center, Bedford Veteran's Affairs Medical Center, Bedford, MA 01730 5 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115

* To whom correspondence should be addressed: Hoon Ryu Department of Neurology Boston University School of Medicine 200 Springs Road Bedford, MA 01730 Tel: 781-687-2922 Fax: 781-687-3515 E-mail: hoonryu{at}bu.edu

Received October 25, 2007; Revised February 29, 2008; Accepted February 29, 2008

Chromatin remodeling is tightly controlled under physiological conditions. Alterations in chromatin structure are involved in the pathogenesis of neuronal systems. We found that the monoallelic deletion of CBP results in the induction of ERG-associated protein with SET domain (ESET) and increases trimethylation of histone H3 (K9) and condensation of pericentromeric heterochromatin structure in neurons. Nested deletion and mutational analysis of the ESET promoter further demonstrated that the Ets-2 transcription factor regulates transcriptional activity of the ESET gene. In CBP+/-mice, Ets-2 occupancy in the ESET promoter DNA was markedly elevated. Our results suggest that CBP is a transcriptional repressor of ESET gene expression by limiting Ets-2 transcriptional activity, while CBP siRNA enhances basal and Ets-2 dependent ESET transcriptional activity. Altered expression of the ESET gene and hypertrimethylation of histone H3 (K9) correlate with striatal neuron atrophy and dysfunction in CBP+/-mice. These results establish an alternative pathway that loss of CBP leads to the pericentric heterochromatin condensation through ESET expression and trimethylation of H3 (K9).


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 FASEB J.Home page
J. Lee, M. Kannagi, R. J. Ferrante, N. W. Kowall, and H. Ryu
Activation of Ets-2 by oxidative stress induces Bcl-xL expression and accounts for glial survival in amyotrophic lateral sclerosis
FASEB J, June 1, 2009; 23(6): 1739 - 1749.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.