A transcriptional insulator at the imprinted H19/Igf2 locus.
Igf2 and H19 exhibit parent-of-origin-specific monoallelic expression. H19 is expressed from the maternal chromosome and Igf2 from the paternal. The two genes share enhancer elements and monoallelic expression of both genes is dependent on cis-acting sequences upstream of the H19 promoter. In this work we examine the mechanisms by which this region silences the maternal Igf2 allele and we demonstrate that deletion of this region can result in high levels of activation of both H19 and Igf2 from a single chromosome. Moreover, by inserting this cis element between a promoter and its enhancer at a heterologous position, we demonstrate that the sequences carry both insulator activity and the ability to be stably imprinted. We also characterize the insulator in vitro and show that it is neither enhancer nor promoter specific.
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 USA. kpfeifer@helix.nih.gov
C R
CR
Kaffer
M
M
Srivastava
K Y
KY
Park
E
E
Ives
S
S
Hsieh
J
J
Batlle
A
A
Grinberg
S P
SP
Huang
K
K
Pfeifer
D000818:Animals; D002874:Chromosome Mapping; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D020868:Gene Silencing; D018392:Genomic Imprinting; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008648:Mesoderm; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000502:physiology; D009154:Mutation; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D014158:Transcription, Genetic; D019076:Transgenes
C094335:H19 long non-coding RNA; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II