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

摘要

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