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Human Molecular Genetics Advance Access originally published online on February 12, 2004
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Human Molecular Genetics, 2004, Vol. 13, No. 7 741-750
DOI: 10.1093/hmg/ddh081

Activating and silencing histone modifications form independent allelic switch regions in the imprinted Gnas gene

Tao Li{dagger}, Thanh H. Vu{dagger}, Gary A. Ulaner, Youwen Yang, Ji-Fan Hu and Andrew R. Hoffman*

Medical Service, Veteran Affairs Palo Alto Health Care System, and Department of Medicine, Stanford University, Palo Alto, CA 94304, USA

Received December 5, 2003; Accepted January 30, 2004

Activation and suppression of gene transcription is tightly controlled by epigenetic modifications. The imprinted Gnas1 gene region contains closely juxtaposed maternally expressed (Nesp) and paternally expressed (Nespas, Gnasxl, Exon 1A) transcripts, providing a unique opportunity to study how epigenetic modifications change in nucleosomes from active to silenced promoters. Using 30 polymorphic sites across the Gnas1 gene region in (C57BL/6JxMus spretus) F1 mice and chromatin immunoprecipitation (ChIP) assays we identified two allelic switch regions (ASRs) that mark boundaries of epigenetic information. We show that activating signals (histone acetylation and methylation of H3 Lys4) and silencing signals (histone methylation of H3 Lys9 and DNA methylation) segregate independently across the ASRs and suggest that these ASRs allow the transcriptional elongation to proceed through the silenced domain of nearby imprinted promoters. We discuss these findings in light of recent progress in the conceptualization of nucleosome remodeling during transcriptional elongation and in the development of histone code.

* To whom correspondence should be addressed. Tel: +1 6504935000 ext. 63930; Fax: +1 6508568024; Email: arhoffman{at}stanford.edu


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