Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1
doi: 10.1242/dev.048181
pmid: 20573698
Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1
A long noncoding RNA, Kcnq1ot1, regulates the expression of both ubiquitously and tissue-specific imprinted genes within the Kcnq1 domain. However, the functional sequences of the Kcnq1ot1 RNA that mediate lineage-specific imprinting are unknown. Here, we have generated a knockout mouse with a deletion encompassing an 890-bp silencing domain (Δ890) downstream of the Kcnq1ot1 promoter. Maternal transmission of the Δ890 allele has no effect on imprinting, whereas paternal inheritance of the deletion leads to selective relaxation of the imprinting of ubiquitously imprinted genes to a variable extent in a tissue-specific manner. Interestingly, the deletion affects DNA methylation at somatically acquired differentially methylated regions (DMRs), but does not affect the histone modifications of the ubiquitously imprinted genes. Importantly, we found that Kcnq1ot1 recruits Dnmt1 to somatic DMRs by interacting with Dnmt1, and that this interaction was significantly reduced in the Δ890 mice. Thus, the ubiquitous and placental-specific imprinting of genes within the Kcnq1 domain might be mediated by distinct mechanisms, and Kcnq1ot1 RNA might mediate the silencing of ubiquitously imprinted genes by maintaining allele-specific methylation through its interactions with Dnmt1.
- Uppsala University Sweden
DNA (Cytosine-5-)-Methyltransferase 1, RNA, Untranslated, Transcription, Genetic, Gene Expression Profiling, Gene Expression Regulation, Developmental, Chromatin, Protein Structure, Tertiary, Genomic Imprinting, Mice, Mutation, Animals, Female, RNA, Long Noncoding, DNA (Cytosine-5-)-Methyltransferases, Gene Silencing, Alleles
DNA (Cytosine-5-)-Methyltransferase 1, RNA, Untranslated, Transcription, Genetic, Gene Expression Profiling, Gene Expression Regulation, Developmental, Chromatin, Protein Structure, Tertiary, Genomic Imprinting, Mice, Mutation, Animals, Female, RNA, Long Noncoding, DNA (Cytosine-5-)-Methyltransferases, Gene Silencing, Alleles
69 Research products, page 1 of 7
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
- 4
- 5
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).253 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
