Novel conserved elements upstream of the H19 gene are transcribed and act as mesodermal enhancers

Robert A. Drewell, Katherine L. Arney, Takahiro Arima, Sheila C. Barton, James D. Brenton, M. Azim Surani

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

The reciprocally imprinted H19 and Igf2 genes form a coordinately regulated 130 kb unit in the mouse controlled by widely dispersed enhancers, epigenetically modified silencers and an imprinting control region (ICR). Comparative human and mouse genomic sequencing between H19 and Igf2 revealed two novel regions of strong homology upstream of the ICR termed H19 upstream conserved regions (HUCs). Mouse HUC1 and HUC2 act as potent enhancers capable of driving expression of an H19 reporter gene in a range of mesodermal tissues. Intriguingly, the HUC sequences are also transcribed bi-allelically in mouse and human, but their expression pattern in neural and endodermal tissues in day 13.5 embryos is distinct from their enhancer function. The location of the HUC mesodermal enhancers upstream of the ICR and H19, and their capacity for interaction with both H19 and Igf2 requires critical re-evaluation of the cis-regulation of imprinted gene expression of H19 and Igf2 in a range of mesodermal tissues. We propose that these novel sequences interact with the ICR at H19 and the epigenetically regulated silencer at differentially methylated region 1 (DMR1) of Igf2.

Original languageEnglish
Pages (from-to)1205-1213
Number of pages9
JournalDevelopment
Volume129
Issue number5
Publication statusPublished - 2002 Aug 23
Externally publishedYes

Keywords

  • Enhancer
  • Genomic imprinting
  • H19
  • HUC
  • Igf2
  • Mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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