Essential role of long non-coding RNAs in de novo chromatin modifications: The genomic address code hypothesis

TL;DR

This paper proposes that long non-coding RNAs serve as genomic address codes, guiding chromatin-modifying enzymes to specific DNA regions to facilitate de novo chromatin modifications during cell differentiation.

Contribution

It introduces the hypothesis that lncRNAs form complexes with enzymes and DNA, providing a molecular mechanism for targeted chromatin modifications based on sequence-specific triple helix formation.

Findings

LncRNAs can form triple helices with DNA at specific genomic sites.

LncRNAs may guide chromatin-modifying enzymes to precise locations.

The diversity of lncRNAs correlates with the need for specific genomic address codes.

Abstract

The epigenome, i.e. the whole of chromatin modifications, is transferred from mother to daughter cells during cell differentiation. When de novo chromatin modifications (establishment or erasure of, respectively, new or pre-existing DNA methylations and/or histone modifications) are made in a daughter cell, however, it has a different epigenome than its mother cell. Although de novo chromatin modifications are an important event that comprises elementary processes of cell differentiation, its molecular mechanism remains poorly understood. We argue in this Letter that a key to solving this problem lies in understanding the role of long non-coding RNAs (lncRNAs)- a type of RNA that is becoming increasingly prominent in epigenetic studies. Many studies show that lncRNAs form ribonucleo-protein complexes in the nucleus and are involved in chromatin modifications. However, chromatin-modifying enzymes lack the information about genomic positions on which they act. It is known, on the other hand, that a single-stranded RNA in general can bind to a double-stranded DNA to form a triple helix. If each lncRNA forms a ribonucleo-protein complex with chromatin-modifying enzymes on one hand and, at the same time, a triple helix with a genomic region based on its specific nucleotide sequence on the other hand, it can induce de novo chromatin modifications at specific sites. Thus, the great variety of lncRNAs can be explained by the requirement for the diversity of "genomic address codes" specific to their cognate genomic regions where de novo chromatin modifications take place.