tailieunhanh - Báo cáo khoa học: Chromosomal protein HMGN1 modulates the expression of N-cadherin

HMGN1 is a nuclear protein that binds to nucleosomes and alters the accessibility of regulatory factors to their chromatin targets. To elucidate its biological function and identify specific HMGN1 target genes, we gener-ated Hmgn1–⁄– mice. DNA microarray analysis of Hmgn1+⁄+ and Hmgn1–⁄– embryonic fibroblasts identified N-cadherin as a potential HMGN1 gene target. | ềFEBS Journal Chromosomal protein HMGN1 modulates the expression of N-cadherin Yaffa R. Rubinstein1 Takashi Furusawa1 Jae-Hwan Lim1 2 Yuri V. Postnikov1 Katherine L. West1 3 Yehudit Birger1 Sunmin Lee4 Phuongmai Nguyen4 Jane B. Trepel4 and Michael Bustin1 1 Laboratory of Metabolism NationalCancer Institute National institutes of Health Bethesda MD USA 2 Department of Biology Andong National university Gyeongsangbuk-do South Korea 3 Division of Cancer Sciences and Molecular Pathology Western Infirmary Pathology University of Glasgow UK 4 MedicalOncology NationalCancer Institute National institutes of Health Bethesda MD USA Keywords HMG protein N-cadherin chromatin transcription Correspondence M. Bustin Laboratory of Metabolism Bldg 37 Room 3122 NCI NIH Bethesda MD 20892 USA Fax 1 301 496 8419 Tel 1 301 496 5234 E-mail bustin@ Received 29 July 2005 revised 7 September 2005 accepted 19 September 2005 doi HMGN1 is a nuclear protein that binds to nucleosomes and alters the accessibility of regulatory factors to their chromatin targets. To elucidate its biological function and identify specific HMGN1 target genes we generated Hmgnl- - mice. DNA microarray analysis of Hmgn1 and Hmgnl- - embryonic fibroblasts identified N-cadherin as a potential HMGN1 gene target. RT-PCR and western blot analysis confirmed a linkage between HMGN1 expression and N-cadherin levels. In both transformed and primary mouse embryonic fibroblasts MEFs HMGN1 acted as negative regulator of N-cadherin expression. Likewise the N-cadherin levels in early embryos of Hmgnl- - mice were higher than those of their Hmgn1 littermates. Loss of HMGN1 increased the adhesiveness motility and aggregation potential of Hmgnl- - MEFs a phenotype consistent with increased levels of N-cadherin protein. Re-expression of wildtype HMGN1 but not of the mutant HMGN1 protein that does not bind to chromatin in Hmgnl- - MEFs decreased the levels of N-cadherin and restored the .

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