Ep400, also known as E1A binding protein p400, is a core catalytic ATPase subunit of ATP-dependent chromatin remodeling complexes [4]. It plays crucial roles in multiple biological processes such as transcription, DNA repair, cell cycle control, and embryonic development [3]. It is involved in histone acetylation and histone dimer exchange activities as part of the TIP60 complex, and deposits histone variants H2AZ and H3.3 into promoters and enhancers during gene activation, contributing to gene regulation [3,5].

In various in vivo studies, Ep400 has shown significant impacts. In mice, depletion of Ep400 in oocytes led to a decline in oocyte quality, abnormal fertilization, reduced major zygotic genome activation, and developmental arrest at the 2-to-4-cell stage [1]. Ep400-deficient Schwann cells in mice caused peripheral neuropathy due to terminal differentiation defects [2]. In oligodendrocytes, deletion of Ep400 at defined development times impaired terminal differentiation, myelination, and led to increased DNA damage and apoptosis [6]. Also, knockdown of Ep400 ortholog in Drosophila increased seizure susceptibility and abnormal neuronal firing, and ep400-deficient zebrafish showed brain developmental abnormalities, epileptic discharges, etc [4].

In conclusion, Ep400 is essential for many biological processes including early embryo development, cell differentiation in the nervous system, and myelination. The gene-knockout and related in vivo models have revealed its significant roles in conditions like peripheral neuropathy, oocyte-related developmental issues, and epilepsy-associated neurodevelopmental disorders, providing valuable insights into understanding the underlying mechanisms and potential therapeutic targets for these diseases.