The SWI/SNF protein ATRX co-regulates pseudoautosomal genes that have translocated to autosomes in the mouse genome

Pseudoautosomal regions (PAR1 and PAR2) in eutherians retain homologous regions between the X and Y chromosomes that play a critical role in the obligatory X-Y crossover during male meiosis. Genes that reside in the PAR1 are exceptional in that they are rich in repetitive sequences and undergo a very high rate of recombination. Remarkably, murine PAR1 homologs have translocated to various autosomes, reflecting the complex recombination history during the evolution of the mammalian X chromosome. We now report that the SNF2-type chromatin remodeling protein ATRX controls the expression of eutherians ancestral PAR1 genes that have translocated to autosomes in the mouse. In addition, we have identified two potentially novel mouse PAR1 orthologs. We propose that the ancestral PAR1 genes share a common epigenetic environment that allows ATRX to control their expression. At E13.5, n = 3 biological replicates of littermate-matched wt/ko pairs. RNA from 2 forebrains were pooled to generate enough RNA for each sample. At P0.5, n = 4 biological replicates of littermate-matched wt/ko pairs (for pair #2 there is one wt and 2 Atrx-null samples (2A & 2B) and we count this as 2 pairs).真兽类（eutherians）的假常染色体区域（Pseudoautosomal regions, PAR1与PAR2）保留了X与Y染色体间的同源序列，此类序列在雄性减数分裂过程中必需的X-Y交换事件中发挥关键作用。定位于PAR1的基因具有显著特殊性：它们富含重复序列，且重组速率极高。值得关注的是，小鼠的PAR1同源序列已易位至多种常染色体，这一现象反映了哺乳动物X染色体进化过程中极为复杂的重组历史。本研究报道，SNF2型染色质重塑蛋白ATRX可调控小鼠中易位至常染色体的真兽类祖先PAR1基因的表达。此外，我们还鉴定出两个潜在的新型小鼠PAR1直系同源基因。我们提出，祖先PAR1基因共享共同的表观遗传环境，这使得ATRX能够调控它们的表达。在胚胎期13.5天（Embryonic day 13.5, E13.5），实验设置n=3组生物学重复，均为同窝匹配的野生型（wild type, WT）/敲除型（knockout, KO）配对；每个样本所需的RNA均通过混合2个前脑的RNA制备获得。在出生后0.5天（Postnatal day 0.5, P0.5），实验设置n=4组生物学重复，均为同窝匹配的WT/KO配对（其中配对#2包含1个WT样本与2个Atrx敲除样本（2A与2B），此处计为2组配对）。