Universität zu Köln

Janzer, Andreas, Stamm, Katrin, Becker, Astrid, Zimmer, Andreas, Buettner, Reinhard and Kirfel, Jutta (2012). The H3K4me3 Histone Demethylase Fbxl10 Is a Regulator of Chemokine Expression, Cellular Morphology, and the Metabolome of Fibroblasts. J. Biol. Chem., 287 (37). S. 30984 - 30993. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

Full text not available from this repository.

Abstract

Fbxl10 (Jhdm1b/Kdm2b) is a conserved and ubiquitously expressed member of the JHDM (JmjC domain-containing histone demethylase) family. Fbxl10 was implicated in the demethylation of H3K4me3 or H3K36me2 thereby removing active chromatin marks and inhibiting gene transcription. Apart from the JmjC domain, Fbxl10 consists of a CxxC domain, a PHD domain, and an Fbox domain. By purifying the JmjC and the PHD domain of Fbxl10 and using different approaches we were able to characterize the properties of these domains in vitro. Our results suggest that Fbxl10 is rather a H3K4me3 than a H3K36me2 histone demethylase. The PHD domain exerts a dual function in binding H3K4me3 and H3K36me2 and exhibiting E3 ubiquitin ligase activity. We generated mouse embryonic fibroblasts stably overexpressing Fbxl10. These cells reveal an increase in cell size but no changes in proliferation, mitosis, or apoptosis. Using a microarray approach we were able to identify potentially new target genes for Fbxl10 including chemokines, the noncoding RNA Xist, and proteins involved in metabolic processes. Additionally, we found that Fbxl10 is recruited to the promoters of Ccl7, Xist, Crabp2, and RipK3. Promoter occupancy by Fbxl10 was accompanied by reduced levels of H3K4me3 but unchanged levels of H3K36me2. Furthermore, knockdown of Fbxl10 using small interfering RNA approaches showed inverse regulation of Fbxl10 target genes. In summary, our data reveal a regulatory role of Fbxl10 in cell morphology, chemokine expression, and the metabolic control of fibroblasts.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Janzer, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Stamm, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Astrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmer, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirfel, Jutta UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-483151
DOI:	10.1074/jbc.M112.341040
Journal or Publication Title:	J. Biol. Chem.
Volume:	287
Number:	37
Page Range:	S. 30984 - 30993
Date:	2012
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language UBIQUITIN LIGASES; DEPENDENT MANNER; BINDING PROTEIN; 1 LSD1; CELLS; PHD; TRANSCRIPTION; APOPTOSIS; DOMAIN; PROLIFERATION Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48315