Non‐coding transcripts in the H19 imprinting control region mediate gene silencing in transgenic Drosophila
Open Access
- 19 October 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Reports
- Vol. 8 (11), 1068-1073
- https://doi.org/10.1038/sj.embor.7401094
Abstract
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.Keywords
This publication has 33 references indexed in Scilit:
- Differential histone modifications mark mouse imprinting control regions during spermatogenesisThe EMBO Journal, 2007
- CTCF binding sites promote transcription initiation and prevent DNA methylation on the maternal allele at the imprinted H19/Igf2 locusHuman Molecular Genetics, 2006
- CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2Proceedings of the National Academy of Sciences of the United States of America, 2006
- Elongation of theKcnq1ot1transcript is required for genomic imprinting of neighboring genesGenes & Development, 2006
- Imprinting on distal chromosome 7 in the placenta involves repressive histone methylation independent of DNA methylationNature Genetics, 2004
- Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexesNature Genetics, 2004
- Interaction between differentially methylated regions partitions the imprinted genes Igf2 and H19 into parent-specific chromatin loopsNature Genetics, 2004
- Transgenic RNAi Reveals Essential Function for CTCF in H19 Gene ImprintingScience, 2004
- The non-coding Air RNA is required for silencing autosomal imprinted genesNature, 2002
- The Prader–Willi Syndrome Imprinting Center Activates the Paternally Expressed Murine Ube3a Antisense Transcript but Represses Paternal Ube3aGenomics, 2001