Phf23 regulates embryonic neurogenesis by increasing the level of H3K27ac of Tcf4 [CUT&Tag]

Epigenetic regulation is an important cell fate modality that is ubiquitous in neural development and plays an important role in both the fate determination and differentiation of neural stem cells (NSCs). The epigenetic regulator Phf23 is widely expressed in different human tissues and is involved in various biological processes, but its functional role in development has rarely been reported. Here, we found that Phf23 is an important epigenetic regulator that maintains embryonic neurogenesis in mice, and its absence leads to inhibition of the acetylation level of H3K27ac through the function of Hdac2, resulting in the blockage of embryonic NSCs differentiation at embryonic day 13.5 (E13.5). Tcf4, a transcription factor closely associated with neurogenesis, is a key downstream target gene of Phf23 in regulating embryonic neurogenesis, which may provide insights into the neuromodulatory network of the brain and the diagnosis and treatment of clinically relevant diseases. To investigate the distribution of H3K27ac on DNA in Phf23+/+ and Phf23-/- NSCs and attempted to find the downstream target genes directly regulated by Phf23 through H3K27ac, we harvested Phf23+/+ and Phf23-/- NSCs for CUT&Tag-seq, 3 replicate samples per group and each group has a negative control. We then performed differentially expressed genes and average H3K27ac bound peak densities in TSS regions using data obtained from CUT&Tag-seq.