R-loop landscapes in the developing human brain are linked to neural differentiation and cell-type specific transcription.

Authors

• Elizabeth A LaMarca
• Atsushi Saito
• Amara Plaza-Jennings
• Sergio Espeso-Gil
• Allyse Hellmich
• Michael B Fernando
• Behnam Javidfar
• Will Liao
• Molly Estill
• Kayla Townsley
• Anna Florio
• James E Ethridge
• Catherine Do
• Benjamin Tycko
• Li Shen
• Atsushi Kamiya
• Nadejda M Tsankova
• Kristen J Brennand
• Schahram Akbarian

Publication/Presentation Date

7-18-2023

Abstract

Here, we construct genome-scale maps for R-loops, three-stranded nucleic acid structures comprised of a DNA/RNA hybrid and a displaced single strand of DNA, in the proliferative and differentiated zones of the human prenatal brain. We show that R-loops are abundant in the progenitor-rich germinal matrix, with preferential formation at promoters slated for upregulated expression at later stages of differentiation, including numerous neurodevelopmental risk genes. RNase H1-mediated contraction of the genomic R-loop space in neural progenitors shifted differentiation toward the neuronal lineage and was associated with transcriptomic alterations and defective functional and structural neuronal connectivity

ISSN

2692-8205

Published In/Presented At

LaMarca, E. A., Saito, A., Plaza-Jennings, A., Espeso-Gil, S., Hellmich, A., Fernando, M. B., Javidfar, B., Liao, W., Estill, M., Townsley, K., Florio, A., Ethridge, J. E., Do, C., Tycko, B., Shen, L., Kamiya, A., Tsankova, N. M., Brennand, K. J., & Akbarian, S. (2023). R-loop landscapes in the developing human brain are linked to neural differentiation and cell-type specific transcription. bioRxiv : the preprint server for biology, 2023.07.18.549494. https://doi.org/10.1101/2023.07.18.549494

Disciplines

Medicine and Health Sciences

PubMedID

37503149

Department(s)

Medical Education

Document Type

Article