Enhancer-Dependent, Locus-Wide Regulation of the Imprinted Mouse Insulin-Like Growth Factor II Gene.

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概要

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• The mouse insulin-like growth factor II (IGF-II) gene is subject to parental imprinting and is predominantly expressed from the paternal chromosome. This allele-specific expression is modified further by cell type, developmental stage, and growth conditions. We show that the ratio of the three major IGF-II mRNAs, each produced from a distinct promoter, is consistent in a variety of tissues and cells representing different modes and phases of the complex regulation. Nuclear run-on assays show that the major changes in total IGF-II mRNA level occur at the level of transcription. Moreover, a targeted disruption of the endoderm-specific enhancers, located 90 kb away from the gene, affects all promoters. The dependency of the promoters on distal enhancers is also shown by transgenesis experiments. Our findings suggest that enhancer-dependent, locus-wide mechanisms play a major role in the coordinate regulation of the multiple IGF-II promoters.

• 社団法人 日本生化学会の論文

著者

• Hatano Naoya

  Division Of Disease Genes Institute Of Genetic Information Kyushu University

• Eversole-cire Pamela

  Department Of Biochemistry And Molecular Biology Usc/norris Comprehensive Cancer Center University O

• Jones Peter

  Department Of Biochemistry And Molecular Biology Usc/norris Comprehensive Cancer Center University O

• Ferguson-smith Anne

  Department Of Anatomy University Of Cambridge

• Sasaki Hiroyuki

  Division Of Biological-regulation And Oncology Department Of Surgery Tohoku University Graduate Scho

• Surani M.

  Welleome/CRC Institute of Cancer and Developmental Biology, University of Cambridge

• Jones Peter

  Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, University of Southern California, School of Medicine

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