Fig. 7: The CRL4B complex directly represses transcription of PPP2R2B and PPP2R2C.
From: CUL4B mutations impair human cortical neurogenesis through PP2A-dependent inhibition of AKT and ERK
A qChIP results showing the enrichment patterns of CUL4B, H2AK119ub1 and H3K27me3 in the promoter of PPP2R2B and PPP2R2C in NPCs. Data are represented as the fold-change over control (IgG). B qChIP analysis of enrichment of CUL4B, H2AK119ub1 and H3K27me3 in PPP2R2B promoter and PPP2R2C promoter in Correct and Patient NPCs. N = 3. Data are presented as the mean ± SEM. The statistical significance was determined using two-tailed unpaired t-test. *: P < 0.05; **: P < 0.01; ***: P < 0.001. ns: no significance. C Schematic showing the mechanism underlying CUL4B regulation of neurogenesis. In wild type NPCs, CRL4B complex cooperates with PRC2 complex to repress transcription of PPP2R2B and PPP2R2C. In NPCs with CUL4B deficiency, PPP2R2B and PPP2R2C are de-repressed, leading to upregulated PP2A complex. PP2A complex then inhibits AKT and ERK, resulting in premature cell cycle exit and precocious neuron differentiation.
