Details

Autor(en) / Beteiligte

• Pappa, Stella
• Padilla, Natalia
• Iacobucci, Simona
• Vicioso, Marta
• de la Campa, Elena Álvarez
• Navarro, Claudia
• Marcos, Elia
• de la Cruz, Xavier
• Martínez-Balbás, Marian A.

Titel

PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2019-09, Vol.116 (39), p.19464-19473

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Histone H3 lysine 9 methylation (H3K9me) is essential for cellular homeostasis; however, its contribution to development is not well established. Here, we demonstrate that the H3K9me2 demethylase PHF2 is essential for neural progenitor proliferation in vitro and for early neurogenesis in the chicken spinal cord. Using genome-wide analyses and biochemical assays we show that PHF2 controls the expression of critical cell cycle progression genes, particularly those related to DNA replication, by keeping low levels of H3K9me3 at promoters. Accordingly, PHF2 depletion induces R-loop accumulation that leads to extensive DNA damage and cell cycle arrest. These data reveal a role of PHF2 as a guarantor of genome stability that allows proper expansion of neural progenitors during development.