Non-coding transcripts in the H19 imprinting control region mediate gene silencing in transgenic Drosophila.
The imprinting control region (ICR) upstream of H19 is the key regulatory element conferring monoallelic expression on H19 and Igf2 (insulin-like growth factor 2). Epigenetic marks in the ICR regulate its interaction with the chromatin protein CCCTC-binding factor and with other control factors to coordinate gene silencing in the imprinting cluster. Here, we show that the H19 ICR is biallelically transcribed, producing both sense and antisense RNAs. We analyse the function of the non-coding transcripts in a Drosophila transgenic system in which the H19 upstream region silences the expression of a reporter gene. We show that knockdown of H19 ICR non-coding RNA (ncRNA) by RNA interference leads to the loss of reporter gene silencing. Our results are, to the best of our knowledge, the first to show that ncRNAs in the H19 ICR are functionally significant, and also indicate that they have a role in regulating gene expression and perhaps epigenetic marks at the H19/Igf2 locus.
Schoenfelder
Stefan
S
Zentrum fuer Molekulare Biologie Heidelberg, Universitaet Heidelberg, INF 282, 69120 Heidelberg, Germany.
Smits
Guillaume
G
Fraser
Peter
P
Reik
Wolf
W
Paro
Renato
R
D000818:Animals; D030801:Animals, Genetically Modified; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D017930:Genes, Reporter; D018392:Genomic Imprinting; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic
C094335:H19 long non-coding RNA; D016376:Oligonucleotides, Antisense; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated