Fig. 6: SETD1B deficiency leads to Pol II redistribution and transcriptional dysregulation.

a Snapshots of the UCSC genome browser showing the normalized ChIP-seq read densities of H3K4me3 across various stages of RSs, along with TAF3 and RNA Pol II read densities from wild-type control and Setd1b cKO bulk RS samples, over the Catsper1 (a broad H3K4me3 target) and Nectin2 (a regular H3K4me3 target) gene loci. Blue shading highlights regions with broad H3K4me3 (left panel) and regular H3K4me3 (right panel) peaks. b MA plots showing changes in RNA Pol II enrichment at the promoter regions of broad H3K4me3 (upper panel) or regular H3K4me3 (lower panel) marked genes following Setd1b depletion. The numbers of broad H3K4me3 targets with decreased Pol II occupancy (loss) and regular H3K4me3 targets with increased Pol II occupancy (gain) are indicated. c Heatmap showing changes in RNA Pol II and TAF3 enrichment on 1341 broad H3K4me3 marked genes exhibiting decreased Pol II occupancy (loss) and 487 regular H3K4me3 marked genes displaying increased Pol II occupancy (gain). The corresponding H3K4me3 enrichment pattern in those regions in wild-type RSs is depicted on the left. d Volcano plot showing differential gene expression between control and Setd1b cKO bulk RSs for broad H3K4me3-marked genes (upper panel) and regular H3K4me3-marked genes (lower panel). Significant differential expression was defined by a threshold of a Log₂ FC ≥ 0.5 or ≤ –0.5, coupled with an adjusted P < 0.05. e Metagene profile plots showing the normalized ChIP-seq read densities of RNA Pol II for down-regulated broad H3K4me3-marked genes and up-regulated regular H3K4me3-marked genes when comparing Setd1b cKO and control bulk RS. f GO analysis for down- and up-regulated genes in bulk RSs when comparing Setd1bcKO and control mice. g Model of SETD1B-mediated broad H3K4me3 regulating gene expression through promoting Pol II occupancy.