Exploring chromatin structural roles of non-coding RNAs at imprinted domains.

David Llères,Robert Feil,Yui Imaizumi

doi:10.1042/bst20210758

Abstract

Different classes of non-coding RNA (ncRNA) influence the organization of chromatin. Imprinted gene domains constitute a paradigm for exploring functional long ncRNAs (lncRNAs). Almost all express an lncRNA in a parent-of-origin dependent manner. The mono-allelic expression of these lncRNAs represses close by and distant protein-coding genes, through diverse mechanisms. Some control genes on other chromosomes as well. Interestingly, several imprinted chromosomal domains show a developmentally regulated, chromatin-based mechanism of imprinting with apparent similarities to X-chromosome inactivation. At these domains, the mono-allelic lncRNAs show a relatively stable, focal accumulation in cis. This facilitates the recruitment of Polycomb repressive complexes, lysine methyltranferases and other nuclear proteins — in part through direct RNA–protein interactions. Recent chromosome conformation capture and microscopy studies indicate that the focal aggregation of lncRNA and interacting proteins could play an architectural role as well, and correlates with close positioning of target genes. Higher-order chromatin structure is strongly influenced by CTCF/cohesin complexes, whose allelic association patterns and actions may be influenced by lncRNAs as well. Here, we review the gene-repressive roles of imprinted non-coding RNAs, particularly of lncRNAs, and discuss emerging links with chromatin architecture.

Highlights

Diverse genetic and epigenetic systems of mono-allelic expression have evolved in mammals, together controlling thousands of genes [1]
Imprinting is controlled by oocyte- and sperm-derived DNA methylation marks put onto specialized CpG islands called ‘imprinting control regions’ (ICRs)
Recent gene targeting studies in mice show that the long-range repressive effects of Airn are not mediated by regulatory sequence elements within the Airn long ncRNAs (lncRNAs) gene, excluding transcriptional interference mechanisms at the distant nonoverlapping genes controlled by Airn

Summary

Review Article

The mono-allelic expression of these lncRNAs represses close by and distant protein-coding genes, through diverse mechanisms. Several imprinted chromosomal domains show a developmentally regulated, chromatin-based mechanism of imprinting with apparent similarities to X-chromosome inactivation. At these domains, the mono-allelic lncRNAs show a relatively stable, focal accumulation in cis. The mono-allelic lncRNAs show a relatively stable, focal accumulation in cis This facilitates the recruitment of Polycomb repressive complexes, lysine methyltranferases and other nuclear proteins — in part through direct RNA–protein interactions. We review the gene-repressive roles of imprinted non-coding RNAs, of lncRNAs, and discuss emerging links with chromatin architecture

Introduction

Gene regulatory roles of imprinted lncRNAs

Emerging roles of imprinted lncRNAs in chromatin architecture