Transcriptional changes upon Mphosph8 or Morc2a loss in sorted neuronal nuclei of adult mouse brains.

We report that murine MPP8 and MORC2A are highly expressed in the brain and exclusively found in neurons. We show that genetic inactivation of Mphosph8 (coding for MPP8) or Morc2a in the nervous system of mice leads to alterations in brain architecture, behavioral impairments and reduction of life span. By doing RNA-seq and ChIP-seq experiments, we found that MPP8 and MORC2A suppress the repetitive-like protocadherin gene cluster on mouse chromosome 18 in a H3K9me3-dependent manner. Examination of consequences of Nestin-Cre-mediated nervous system-specific knock-out of Mphosph8 and Morc2a in FACS-sorted neuronal nuclei (from at least 2 brains per genotype).本研究报道，小鼠MPP8与MORC2A在大脑中呈高表达，且仅特异性分布于神经元内。我们证实，在小鼠神经系统中对编码MPP8的Mphosph8基因或Morc2a基因进行遗传失活，可引发大脑结构异常、行为障碍以及寿命缩短。通过RNA测序（RNA-seq）与染色质免疫共沉淀测序（ChIP-seq）实验，我们发现MPP8与MORC2A能够以依赖于组蛋白H3赖氨酸9三甲基化（H3K9me3）的方式，抑制小鼠18号染色体上的类重复原钙粘蛋白基因簇。本研究还对经巢蛋白-Cre（Nestin-Cre）介导的Mphosph8与Morc2a神经系统特异性敲除小鼠的荧光激活细胞分选（FACS）纯化神经元细胞核（每个基因型至少取2个脑组织样本）的相关后果进行了检测。