English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Background  Gene regulation in eukaryotes is a complex process entailing the establishment of transcriptionally silent chromatin domains interspersed with regions of active transcription. Imprinted domains consist of clusters of genes, some of which exhibit parent-of-origin dependent monoallelic expression, while others are biallelic. The  Kcnq1  imprinted domain illustrates the complexities of long-range regulation that coexists with local exceptions. A paternally expressed repressive non-coding RNA,  Kcnq1ot1 , regulates a domain of up to 750 kb, encompassing 14 genes. We study how the  Kcnq1  gene, initially silenced by  Kcnq1ot1 , undergoes tissue-specific escape from imprinting during development. Specifically, we uncover the role of chromosome conformation during these events.    Results  We show that  Kcnq1  transitions from monoallelic to biallelic expression during mid gestation in the developing heart. This transition is not associated with the loss of methylation on the  Kcnq1  promoter. However, by exploiting chromosome conformation capture (3C) technology, we find tissue-specific and stage-specific chromatin loops between the  Kcnq1  promoter and newly identified DNA regulatory elements. These regulatory elements showed  in vitro  activity in a luciferase assay and  in vivo  activity in transgenic embryos.    Conclusions  By exploring the spatial organization of the  Kcnq1  locus, our results reveal a novel mechanism by which local activation of genes can override the regional silencing effects of non-coding RNAs.

Enhancer-driven chromatin interactions during development promote escape from silencing by a long non-coding RNA