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

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.

PLIC11 drives lung cancer progression through regulating the YY1/PIWIL4 axis

“…In our study, we conducted high‐throughput sequencing technology to analyze these two cells. Growing evidence suggest that a few lncRNAs that regulate neighboring gene act preferentially in cis, and those cis ‐encode elements, such as RNA transcripts or sequence motifs, 6 interact with a variety of regulators to module canonical regulatory mechanisms 18 . First, we analyzed the differential‐expression lncRNAs between SPC‐A‐1sci and SPC‐A‐1 cells (the fold of change >2).…”

“…Growing evidence suggest that a few lncRNAs that regulate neighboring gene act preferentially in cis, and those cis-encode elements, such as RNA transcripts or sequence motifs, 6 interact with a variety of regulators to module canonical regulatory mechanisms. 18 First, we analyzed the differential-expression lncRNAs between SPC-A-1sci and SPC-A-1 cells (the fold of change >2). After cis-action bioinformatic analysis, we mainly focused on 44 differentialexpression lncRNAs that may be involved in cis regulation (Figure 1A).…”

Genomic Imprinting in the New Omics Era: A Model for Systems-Level Approaches

“…The regulation of gene expression in imprinting clusters is provided in particular by lncRNAs, which are located in the immediate vicinity of ICRs and have an effect on large physical distances within clusters. Their precise roles need further clarification, but it is accepted that lncRNAs do more than simple transcriptional interference and are required for imprinting maintenance ( MacDonald and Mann, 2020 ; Llères et al, 2021 ). As such RNAs may exceed one kilobase in length, the use of direct RNA-seq methods compatible with long reads appears an appropriate strategy to favor their characterization while limiting the occurrence of bias ( Garalde et al, 2018 ).…”

Livestock species as emerging models for genomic imprinting

“…Our understanding of how regions affected by imprinting have evolved and function has expanded considerably ( Llères et al, 2021 ; Kaneko-Ishino and Ishino, 2022 ; Richard Albert et al, 2023 ) and we today have increasingly sophisticated resources and tools ( Hubert and Demars, 2022 ; Jima et al, 2022 ; Akbari et al, 2023 ) to identify and accurately report the links between nuclear architecture, Imprinting Control Regions (ICRs), imprinted genes, other genes including different RNA species and, finally, phenotypes. While cytosine methylation is key to almost all regulations that affect it, including transgenerational maintenance, imprinting involves multi-scale mechanisms ( Monk et al, 2019 ), giving grounds for multi-omics approaches ( Hubert and Demars, 2022 ).…”