ZFP57 is a regulator of postnatal growth and life-long health

Early-life factors, including postnatal nutrition, shape long-term health outcomes with epigenetic effects being implicated but poorly understood in the process. Zinc-finger protein 57 (ZFP57), is an epigenetic regulator of genomic imprinting, a process controlling gene expression based on parental origin with a vital role in prenatal growth. Here, we report an imprinting-independent function of ZFP57 in postnatal resource control via the mammary gland. ZFP57 influences multiple mammary gland phenotypes, including ductal branching and cellular homeostasis with its absence leading to significant differential gene expression related to alveologenesis and lactogenesis and altered milk composition. Zfp57^-/- dams attenuate offspring growth, with impacts on offspring metabolic health; effects exacerbated when pups are raised by a dam of a different genotype than their birth mother. The study identifies ZFP57 as a major regulator of both pre and postnatal resource control in mammals, offering new insights into early factors influencing lifelong health.