The Kcnq1ot1 Long Non-Coding RNA Affects Chromatin Conformation and Expression of Kcnq1, but Does Not Regulate Its Imprinting in the Developing Heart

• DOI: 10.1371/journal.pgen.1002956
• Publication Date: 2012-09-20T17:55:47Z
• Authors: Lisa Korostowski; Natalie Sedlak; Nora Engel
• Keywords: Genomic Imprinting; Imprinting (psychology)

Although many of the questions raised by discovery imprinting have been answered, we not yet accounted for tissue- or stage-specific imprinting. The Kcnq1 imprinted domain exhibits complex tissue-specific expression patterns co-existing with a domain-wide cis-acting control element. Transcription paternally expressed antisense non-coding RNA Kcnq1ot1 silences some neighboring genes in embryo, while others are unaffected. is early cardiac development but becomes biallelic after midgestation. To explore this phenomenon and role Kcnq1ot1, used allele-specific assays chromosome conformational studies wild-type mice premature termination mutation Kcnq1ot1. We show that heart established maintained independently expression, thus excluding repressing Kcnq1, even silencing other domain. exact timing mono- to transition strain-dependent, CAST/EiJ allele becoming activated earlier acquiring higher levels than C57BL/6J allele. Unexpectedly, itself also switches specifically heart, suggesting loss may be common during embryogenesis. maternal transcript shorter paternal ncRNA, its activation depends on an alternative transcriptional start site bypasses maternally methylated promoter. Production does silence Cdkn1c. find later developmental stages, however, has modulating levels, since absence leads overexpression event accompanied aberrant three-dimensional structure chromatin. Thus, our reveal regulatory mechanisms within operate exclusively gene crucial function. uncover novel mechanism which affects transcription through regulating chromatin flexibility access enhancers.