Regulation of Gene Expression and Replication Initiation by Non‐Coding Transcription: A Model Based on Reshaping Nucleosome‐Depleted Regions

Abstract

RNA polymerase II (RNAP II) non-coding transcription is now known to cover almost the entire eukaryotic genome, a phenomenon referred to as pervasive transcription. As a consequence, regions previously thought to be non-transcribed are subject to the passage of RNAP II and its associated proteins for histone modification. This is the case for the nucleosome-depleted regions (NDRs), which provide key sites of entry into the chromatin for proteins required for the initiation of coding gene transcription and DNA replication. In this review, recent data on the effects of pervasive transcription through NDRs are summarized and a model is proposed to explain how RNAP II-driven transcription is able to modify the nucleosomes flanking the NDRs, leading to nucleosome repositioning and NDR closure. Even though much of the mechanistic detail underlying these events remains to be elucidated, such a model provides a basis to explain how non-coding transcription through NDRs can regulate the initiation of coding gene expression and DNA replication.

Pervasive transcription of the mitochondrial genome in Candida albicans is revealed in mutants lacking the mtEXO RNase complex

“…The loss of mtEXO activity reveals the existence of transcripts covering the majority of the genome, consistent with pervasive transcription demonstrated in the Eukaryotic nucleus [ 3 , 5–7 , 86 , 87 ], and in Prokaryotes [ 4 , 88 , 89 ]. Significant amounts of noncoding RNAs mapping outside annotated genes were also identified in plant organelle transcriptomes, mostly in chloroplasts [ 90–93 ].…”

Fine Chromatin-Driven Mechanism of Transcription Interference by Antisense Noncoding Transcription

“…Replication defects induced by noncoding transcription readthrough into ARS NDR can be partially rescued in the absence of Set2. Although we did not have a precise mechanism in our previous study, the similarity between these earlier observations and the present ones tend to converge in a unique model that may be applicable to all types of NDRs (Soudet and Stutz, 2019).…”

Antisense-mediated repression of SAGA-dependent genes involves the HIR histone chaperone

“…Second, the transcription of many long non-coding RNAs (lncRNAs) overlaps with functional elements such as promoters of coding genes, potentially leading to Transcription Interference (TI) i.e. repression of the coding gene (13).…”

“…Transcription of lncRNAs can invade coding gene promoters either in tandem or in antisense configurations with respect to the coding gene. High levels of nascent antisense transcription into promoters in Eukaryotes correlate with significantly lower levels of coding sense transcription (13)(14)(15). Thus, we recently proposed antisense transcription as one parameter significantly regulating 20% of the S. cerevisiae coding genes (16).…”