Genome-wide R-loop Landscapes during Cell Differentiation and Reprogramming.
Cell Rep
; 32(1): 107870, 2020 07 07.
Article
in En
| MEDLINE
| ID: mdl-32640235
ABSTRACT
DNARNA hybrids play key roles in both physiological and disease states by regulating chromatin and genome organization. Their homeostasis during cell differentiation and cell plasticity remains elusive. Using an isogenic human stem cell platform, we systematically characterize R-loops, DNA methylation, histone modifications, and chromatin accessibility in pluripotent cells and their lineage-differentiated derivatives. We confirm that a portion of R-loops formed co-transcriptionally at pluripotency genes in pluripotent stem cells and at lineage-controlling genes in differentiated lineages. Notably, a subset of R-loops maintained after differentiation are associated with repressive chromatin marks on silent pluripotency genes and undesired lineage genes. Moreover, in reprogrammed pluripotent cells, cell-of-origin-specific R-loops are initially present but are resolved with serial passaging. Our analysis suggests a multifaceted role of R-loops in cell fate determination that may serve as an additional layer of modulation on cell fate memory and cell plasticity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genome, Human
/
Cell Differentiation
/
Cellular Reprogramming
/
R-Loop Structures
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2020
Document type:
Article
Affiliation country:
China