Maternal-specific footprints at putative CTCF sites in the H19 imprinting control region give evidence for insulator function

Curr Biol. 2000 May 18;10(10):607-10. doi: 10.1016/s0960-9822(00)00489-9.


Parent-of-origin-specific expression of the mouse insulin-like growth factor 2 (Igf2) gene and the closely linked H19 gene are regulated by an intervening 2 kb imprinting control region (ICR), which displays parentspecific differential DNA methylation [1] [2]. Four 21 bp repeats are embedded within the ICR and are conserved in the putative ICR of human and rat Igf2 and H19, suggesting that the repeats have a function [3] [4]. Here, we report that prominent DNA footprints were found in vivo on the unmethylated maternal ICR at all four 21 bp repeats, demonstrating the presence of protein binding. The methylated paternal ICR displayed no footprints. Significantly, the maternal-specific footprints were localized to putative binding sites for CTCF, a highly conserved zinc-finger DNA-binding protein with multiple roles in gene regulation including that of chromatin insulator function [5] [6]. These results strongly suggest that the maternal ICR functions as an insulator element in regulating mutually exclusive expression of Igf2 and H19 in cis.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromatin / chemistry*
  • Chromatin / genetics
  • DNA Footprinting*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • Genomic Imprinting*
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism
  • Male
  • Mice
  • Mothers
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • RNA, Long Noncoding
  • RNA, Untranslated*
  • Rats


  • Chromatin
  • DNA-Binding Proteins
  • H19 long non-coding RNA
  • Muscle Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Insulin-Like Growth Factor II