Transcriptional profiling of Setd5 mutant cortical tissue

Setd5 inactivation in neural stem cells, zebrafish and mouse leads to a significant H3K36 hypo-methylation mostly detectable along the gene bodies. Consequently, this chromatin alteration perturbs RNA processing during elongation, compromising the transcriptional output. This gene dysregulation affects proliferative dynamics of NSCs and synaptic wiring in the neuronal derivatives, ultimately resulting in behavioral deficits in adult mice. 3 wt and 3 Setd5 heterozygous adult cortex在神经干细胞、斑马鱼与小鼠中使Setd5基因失活，可引发显著的H3K36低甲基化（H3K36 hypo-methylation），该表观修饰主要可在基因体区域被检测到。此种染色质改变会干扰转录延伸过程中的RNA加工，进而损害转录输出水平。该基因表达失调会影响神经干细胞（Neural Stem Cells，简称NSCs）的增殖动态，并干扰神经元子代细胞的突触连接构建，最终导致成年小鼠出现行为缺陷。3份野生型及3份Setd5杂合子成年小鼠的皮层组织