ZNF445 is a primary regulator of genomic imprinting

ZFP445/ZNF445 collaborates with ZFP57 to control genomic imprinting in vivo in mouse and in human embryonic stem cells. We determined that ZNF445/ZFP445, a KZFP that can be traced back to marsupials, binds human and murine ICRs, and together with ZFP57 correctly maintains all but one murine ICR in vivo. Furthermore, the early embryonic expression of human ZNF445 and its intolerance to loss of function mutations in the population suggest a critical role in human development. Overall design: Study of ZFP445 ChIP-seq in different mouse genomic backgrounds and ZFP57 and KAP1 ChIP-seq in human. All with their respective inputs.ZFP445/ZNF445可与ZFP57协同，在小鼠体内及人类胚胎干细胞中调控基因组印记（genomic imprinting）。本研究证实，ZNF445/ZFP445作为一种可追溯至有袋类动物的KRAB型锌指蛋白（KZFP），能够结合人类与小鼠的印记控制区（ICRs），并可与ZFP57共同在体内正确维持除单个小鼠印记控制区之外的所有印记控制区的稳态。此外，人类ZNF445的早期胚胎表达特征，以及其在人群中对功能丧失突变的不耐受性，均提示其在人类胚胎发育过程中发挥关键作用。总体实验设计：针对不同小鼠基因组背景下的ZFP445染色质免疫共沉淀测序（ChIP-seq）实验，以及人类样本中ZFP57与KAP1的ChIP-seq实验开展研究，所有实验均设置了对应的Input对照样本。