The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes.

作者: Daniel Andergassen , Markus Muckenhuber , Philipp C. Bammer , Tomasz M. Kulinski , Hans-Christian Theussl

DOI: 10.1371/JOURNAL.PGEN.1008268

关键词: Gene silencingChromosome conformation captureEnhancerGeneticsGeneLocus (genetics)Regulation of gene expressionBiologyGenomic imprintingPromoter

摘要: Long non-coding (lnc) RNAs are numerous and found throughout the mammalian genome, many thought to be involved in regulation of gene expression. However, majority remain relatively uncharacterised uncertain function making use model systems uncover their mode action valuable. Imprinted lncRNAs target recruit epigenetic silencing factors a cluster imprinted genes on same chromosome, them one best characterized for distant cis. In this study we examined Slc22a3 by lncRNA Airn Igf2r mouse. Previously proposed that may silence disrupting promoter-enhancer interactions being transcribed through enhancer, which called enhancer interference hypothesis. Here tested hypothesis first using allele-specific chromosome conformation capture (3C) detect between promoter locus silences it paternal chromosome. agreement with model, enriched maternal allele across entire consistent multiple enhancer-promoter interactions. Therefore, test devised an approach delete gene. deletion showed there no essential enhancers Slc22a2, Pde10a within gene, strongly indicating RNA rather than its transcription is responsible genes. Furthermore, silent were covered large blocks H3K27me3 repressed allele. Therefore propose alternative whereby initially guide promoters repressive chromatin, these lost once established.

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