a Central Clinical School, Faculty of Medicine , Monash University , Victoria , Australia.
b Baker IDI Heart and Diabetes Institute , The Alfred Medical Research and Education Precinct , Melbourne , Victoria 3004 , Australia.
Epigenetics. 2017;12(12):1028-1037. doi: 10.1080/15592294.2017.1391429.
Although methyl CpG binding domain protein-2 (MeCP2) is commonly understood to function as a silencing factor at methylated DNA sequences, recent studies also show that MeCP2 can bind unmethylated sequences and coordinate gene activation. MeCP2 displays broad binding patterns throughout the genome, with high expression levels similar to histone H1 in neurons. Despite its significant presence in the brain, only subtle gene expression changes occur in the absence of MeCP2. This may reflect a more complex regulatory mechanism of MeCP2 to complement chromatin binding. Using an RNA immunoprecipitation of native chromatin technique, we identify MeCP2 interacting microRNAs in mouse primary cortical neurons. In addition, comparison with mRNA sequencing data from Mecp2-null mice suggests that differentially expressed genes may indeed be targeted by MeCP2-interacting microRNAs. These findings highlight the MeCP2 interaction with microRNAs that may modulate its binding with chromatin and regulate gene expression.
虽然甲基化 CpG 结合域蛋白-2（MeCP2）通常被认为是在甲基化 DNA 序列上起沉默因子的作用，但最近的研究也表明 MeCP2 可以结合非甲基化序列并协调基因激活。MeCP2 在整个基因组中表现出广泛的结合模式，其表达水平与神经元中的组蛋白 H1 相似。尽管 MeCP2 在大脑中大量存在，但在没有 MeCP2 的情况下，只有细微的基因表达变化发生。这可能反映了 MeCP2 更复杂的调控机制来补充染色质结合。使用天然染色质的 RNA 免疫沉淀技术，我们在小鼠原代皮质神经元中鉴定出与 MeCP2 相互作用的 microRNAs。此外，与 Mecp2 缺失小鼠的 mRNA 测序数据进行比较表明，差异表达的基因可能确实是由 MeCP2 相互作用的 microRNAs 靶向的。这些发现强调了 MeCP2 与 microRNAs 的相互作用，这可能调节其与染色质的结合并调节基因表达。
