The role of chromatin-mediated regulation in cell-fate specification during mammalian development is been increasingly appreciated. However, very little is known about epigenetic regulatory networks during embryonic neurogenesis. In search for novel epigenetic regulators of neuronal development, we find that Phf21b is specifically expressed in the cortex during embryonic neurogenesis. Interestingly, knockdown of Phf21b during cortical development leads to a defective neurogenesis. Immunoprecipitation assay combined with mass-spectrometry revealed that Phf21b associates with the repressive chromatin machinery including histone deacetylases as well as Lsd1, suggesting that it likely functions in gene repression. Biochemical analysis revealed that Phf21b has higher affinity for H3K4me1 compared to other modifications states of histone H3 at Lysine 4 (K4). Our data suggests that Phf21b targets the regulatory regions of the cell cycle genes where they recruit Lsd1 and Hdac2 to repress them via loss of H3K4me1 and H3K27ac. Overall, we identify Phf21b as a novel essential regulator of neurogenesis, which mediates epigenetic silencing of cell cycle genes during cortical development. SOURCE: Hyobin Jeong (h.jeong@imb-mainz.de) -  IMB

Pluto Bioinformatics

GSE106999: Phf21b is a novel histone reader essential for epigenetic silencing of cell cycle genes during neurogenesis