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

Epigenetics & Chromatin

Nora Engel¹  Gillian Breuer¹  Anjali Raval¹  Lisa Korostowski¹ 

[1] Fels Institute for Cancer Research & Molecular Biology & Department of Biochemistry, Pharmacy Building, Room 201, Temple University School of Medicine, Philadelphia, PA 19104, USA

关键词: chromosome conformation capture (3C);    Kcnq1;    Kcnq1ot1;    non-coding RNAs;    Imprinting;   

Others  :  813838
DOI  :  10.1186/1756-8935-4-21

 received in 2011-09-16, accepted in 2011-11-15,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Korostowski et al; licensee BioMed Central Ltd.

【 图 表 】

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