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Significance During early neurogenesis, progenitors maintain the balance between self-renewal and differentiation. This equilibrium is preserved by the coordinated action of developmental cues and epigenetic mechanisms. We analyzed the role of the H3K9me2 histone demethylase PHF2 in neural stem cells biology in vitro and in early neurogenesis in the chicken neural tube. We found that PHF2 is essential for proliferation of progenitors. Additionally, PHF2 maintains the genome integrity, preventing R-loop accumulation and DNA damage. Our work contributes to the clarification of both the physiological and molecular roles of PHF2 during early neurogenesis. It opens avenues to understand the role of H3K9 methylation not only in development but also in diseases such as autism, cancer, and obesity where PHF2 has been involved.

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