Schematic model of the two mechanisms for the establishment of accessible chromatin in the promoter and distal regions. (A) Enrichment of unmethylated CpGs that are inherited from the sperm and oocyte primes the formation of accessible promoters during ZGA, which is mediated by CXXC domain-containing factors, such as Cxxc1b. (B) Paternally inherited DNA hypermethylation facilitates the binding of DNA methylation-preferred transcription factors, such as Pou5f3 and Nanog, and these factors recruit Smarca4a and contribute to the formation of accessible distal regions during ZGA. Such factors may participate in Tet-mediated demethylation and, in turn, lead to an oocyte-like DNA hypomethylation pattern after ZGA.