Universität zu Köln

Schwer, Bjoern, Schumacher, Bjoern, Lombard, David B., Xiao, Cuiying, Kurtev, Martin V., Gao, Jun, Schneider, Jennifer I., Chai, Hua, Bronson, Roderick T., Tsai, Li-Huei, Deng, Chu-Xia and Alt, Frederick W. (2010). Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity. Proc. Natl. Acad. Sci. U. S. A., 107 (50). S. 21790 - 21795. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

In yeast, Sir2 family proteins (sirtuins) regulate gene silencing, recombination, DNA repair, and aging via histone deacetylation. Most of the seven mammalian sirtuins (Sirt1-Sirt7) have been implicated as NAD(+)-dependent protein deacetylases with targets ranging from transcriptional regulators to metabolic enzymes. We report that neural-specific deletion of sirtuin 6 (Sirt6) in mice leads to postnatal growth retardation due to somatotropic attenuation through low growth hormone (GH) and insulin-like growth factor 1 (IGF1) levels. However, unlike Sirt6 null mice, neural Sirt6-deleted mice do not die from hypoglycemia. Instead, over time, neural Sirt6-deleted mice reach normal size and ultimately become obese. Molecularly, Sirt6 deletion results in striking hyperacetylation of histone H3 lysine 9 (H3K9) and lysine 56 (H3K56), two chromatin marks implicated in the regulation of gene activity and chromatin structure, in various brain regions including those involved in neuroendocrine regulation. On the basis of these findings, we propose that Sirt6 functions as a central regulator of somatic growth and plays an important role in preventing obesity by modulating neural chromatin structure and gene activity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schwer, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Lombard, David B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Xiao, Cuiying UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurtev, Martin V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gao, Jun UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Jennifer I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chai, Hua UNSPECIFIED UNSPECIFIED UNSPECIFIED Bronson, Roderick T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsai, Li-Huei UNSPECIFIED UNSPECIFIED UNSPECIFIED Deng, Chu-Xia UNSPECIFIED UNSPECIFIED UNSPECIFIED Alt, Frederick W. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-490652
DOI:	10.1073/pnas.1016306107
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	107
Number:	50
Page Range:	S. 21790 - 21795
Date:	2010
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION; NERVOUS-SYSTEM; HISTONE; DEACETYLATION; DISRUPTION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49065