Abstract
ABSTRACTIgf2, H19, and Nctc1 are linked co-regulated genes on distal mouse chromosome 7. This locus is an important model both for studying mechanisms of monoallelic expression and for elucidating the role of cis-regulatory elements – enhancers and insulators – in organizing chromatin and gene expression across a large domain. In this study we characterize regulated expression of the Igf2 antisense transcript (Igf2as) in primary muscle cells. We demonstrate that Igf2as is imprinted (expressed only from the paternal chromosome). We also show that Igf2as expression during differentiation follows the same patterns as Igf2 and H19. Moreover, this expression is dependent upon the same shared enhancer element. Thus, our work shows that the imprinted cluster includes Igf2as in addition to H19, Igf2, and Nctc1.
Highlights
Genomic imprinting is a regulatory system in mammals where gene expression is determined by parental origin
We have recently shown that Nctc1 lnRNA expression is dependent upon this shared Igf2/H19 enhancer element and that Nctc1 transcription is biased about 4:1 toward the paternal allele because the Nctc1 promoter must compete with H19 and with Igf2 for access to the shared enhancer
We confirmed that expression of Igf2 antisense transcript (Igf2as) is paternally biased and we show that expression is dependent upon the shared muscle enhancer element that drives expression of H19, Igf2, and Nctc1
Summary
Genomic imprinting is a regulatory system in mammals where gene expression is determined by parental origin. It is unclear whether Igf2as shares the skeletal muscle enhancer with H19, Igf2 and Nctc1. We compared expression of Igf2as with H19, Igf2 and Nctc1 in primary myoblasts and in differentiating myotubes.
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