The Cumulative Formation of R-loop Interacts with Histone Modifications to Shape Cell Reprogramming

R-loop, a three-stranded RNA/DNA structure, plays important roles in modulating genome stability and gene expression, but the molecular mechanism of R-loops in cell reprogramming remains elusive. Here, we comprehensively profiled the genome-wide landscape of R-loops during cell reprogramming. The re...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-01, Vol.23 (3), p.1567
Main Authors: Li, Hanshuang, Long, Chunshen, Hong, Yan, Chao, Lemuge, Peng, Yong, Zuo, Yongchun
Format: Article
Language:English
Subjects:
Animals
Cell cycle
Cell fate
Cellular Reprogramming - genetics
DNA structure
Epigenetics
Gene expression
Gene Expression Regulation, Developmental
Gene Regulatory Networks
Genome
Genomes
Histone Code - genetics
Histones
Mice
Pluripotency
Pluripotent Stem Cells - metabolism
R-Loop Structures - genetics
R-loops
Stem cells
Transcription activation
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Summary:R-loop, a three-stranded RNA/DNA structure, plays important roles in modulating genome stability and gene expression, but the molecular mechanism of R-loops in cell reprogramming remains elusive. Here, we comprehensively profiled the genome-wide landscape of R-loops during cell reprogramming. The results showed that the R-loop formation on most different types of repetitive elements is stage-specific in cell reprogramming. We unveiled that the cumulative deposition of an R-loop subset is positively correlated with gene expression during reprogramming. More importantly, the dynamic turnover of this R-loop subset is accompanied by the activation of the pluripotent transcriptional regulatory network (TRN). Moreover, the large accumulation of the active histone marker H3K4me3 and the reduction in H3K27me3 were also observed in these R-loop regions. Finally, we characterized the dynamic network of R-loops that facilitates cell fate transitions in reprogramming. Together, our study provides a new clue for deciphering the interplay mechanism between R-loops and HMs to control cell reprogramming.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23031567