PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors.
Stella PappaNatalia PadillaSimona IacobucciMarta ViciosoElena Álvarez de la CampaClaudia NavarroElia MarcosXavier de la CruzMarian A Martínez-BalbásPublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
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.
Keyphrases
- cell cycle
- genome wide
- dna damage
- dna methylation
- cell proliferation
- cell cycle arrest
- spinal cord
- copy number
- oxidative stress
- pi k akt
- dna repair
- cell death
- gene expression
- poor prognosis
- signaling pathway
- transcription factor
- big data
- long non coding rna
- single cell
- mouse model
- data analysis
- artificial intelligence
- bioinformatics analysis