A SCAN-box containing KRAB-ZFP maintains DNA methylation and inhibits gene expression [RRBS]

DNA methylation is one of the most characteristic epigenetic modifications. In mammals, it is involved in a variety of biological processes, including transposable element silencing, gene expression regulation, genomic imprinting, and X chromosome inactivation. Here, through a medium-scale analysis of CpG islands loci coupled with ChIP-seq of Krüppel associated box zinc finger proteins (KRAB-ZFPs), we identified a murine ZFP, ZFP202, that bind to methylated CpG loci. We found that ZFP202 not only maintain CpG loci methylation, but also inhibit downstream gene expression in specific tissues. Disruption of ZFP202 in mouse led to genes upregulation in testis and placenta. Thus, our research identified a novel transcription factor that binding to methylated DNA and maintaining DNA methylation and promoting gene inhibition. As ZFP202 is highly expressed in brain, testis and placenta, we harvested genomic DNA from adult testis, 12.5 embryo days (E12.5) placenta and whole brain of Zfp202 KO and WT mice, respectively. We then performed reduced representation bisulfite sequencing (RRBS) after MspI digestion of genomic DNA.