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Control of mouse U1a and U1b snRNA gene expression by differential transcription Open Access
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small nuclear RNA
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The expression of mouse embryonic U1 snRNA (mU1b) genes is subject to stage- and tissue-specific control, being restricted to early embryos and adult tissues that contain a high proportion of stem cells capable of further differentiation. To determine the mechanism of this control we have sought to distinguish between differential RNA stability and regulation of U1 gene promoter activity in several cell types. We demonstrate here that mU1b RNA can accumulate to high levels in permanently transfected mouse 3T3 and C127 fibroblast cells which normally do not express the endogenous 1Mb genes, and apparently can do so without significantly Interfering with cell growth. Expression of transfected chlmerlc U1 genes in such cells Is much more efficient when their promoters are derived from a constitutlvely expressed mU1a gene rather than from an mU1b gene. In transgenic mice, introduced U1 transgenes with an mU1b 5' flanking region are subject to normal tissue-specific control, indicating that 1Mb promoter activity is restricted to tissues that normally express 1Mb genes. Inactivation of the embryonic genes during normal differentiation is not associated with methylation of upstream CpGrich sequences; however, in NIH 3T3 fibroblasts, the 5' flanking regions of endogenous mlMb genes are completely methylated, indicating that DNA methylation serves to Imprint the inactive state of the mLM b genes In cultured cells. Based on these results, we propose that the developmental control of 1Mb gene expression is due to differential activity of mU1a and mU1b promoters rather than to differential stability of U1a and 1Mb RNAs.
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JF Caceres, DI McKenzie, R Thimappaya, E Lund and JE Dahlberg. "Control of mouse U1a and U1b snRNA gene expression by differential transcription." Nucleic Acids Research 20 (1992): 4247-4254. DOI: 10.1093/nar/20.16.4247
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