Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes

Debora Mancini-DiNardo, Scott J.S. Steele, John M. Levorse, Robert S. Ingram, Shirley M. Tilghman

Research output: Contribution to journalArticle

324 Scopus citations

Abstract

The imprinted gene cluster at the telomeric end of mouse chromosome 7 contains a differentially methylated CpG island, KvDMR, that is required for the imprinting of multiple genes, including the genes encoding the maternally expressed placental-specific transcription factor ASCL2, the cyclin-dependent kinase CDKN1C, and the potassium channel KCNQ1. The KvDMR, which maps within intron 10 of Kcnq1, contains the promoter for a paternally expressed, noncoding, antisense transcript, Kcnq1ot1. A 244-base-pair deletion of the promoter on the paternal allele leads to the derepression of all silent genes tested. To distinguish between the loss of silencing as the consequence of the absence of transcription or the transcript itself, we prematurely truncated the Kcnq1ot1 transcript by inserting a transcriptional stop signal downstream of the promoter. We show that the lack of a full-length Kcnq1ot1 transcript on the paternal chromosome leads to the expression of genes that are normally paternally repressed. Finally, we demonstrate that five highly conserved repeats residing at the 5′ end of the Kcnq1ot1 transcript are not required for imprinting at this locus.

Original languageEnglish (US)
Pages (from-to)1268-1282
Number of pages15
JournalGenes and Development
Volume20
Issue number10
DOIs
StatePublished - May 15 2006

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Keywords

  • DNA methylation
  • Genomic imprinting
  • Kcnq1ot1
  • Noncoding RNA
  • RNA-dependent silencing

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    Mancini-DiNardo, D., Steele, S. J. S., Levorse, J. M., Ingram, R. S., & Tilghman, S. M. (2006). Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes and Development, 20(10), 1268-1282. https://doi.org/10.1101/gad.1416906