UHRF2 Affects DNA 5-Methylcytosine Hydroxylation And Acquisition Of Murine Learning And Memory

DNA methylation is an important part of research on epigenetics. UHRF1 can recruit DNMT1 to DNA replication foci through SRA domain, then methylatenewly synthesized DNA to maintain DNA methylation. UHRF1 also binds methylated histone H3 lysine 9 (H3K9) through its TTD domain. When 187 and proline 188 of TTD domain were mutated in mouse, UHRF1 failed to bind H3K9me2/3, and global DNA methylation was decreased by about 10%, therefore regulating DNA methylation.UHRF2 is a homologous to UHRF1, the two proteins are similar in sequence and arrangement of structural domains. As we have known, like UHRF1, UHRF2 is also an ubiquitin lagase, but the function of UHRF2 is unclear. Can UHRF2 regulate DNA methylation?In order to investigate this, UHRF2 knockout mice were constructed. The mice could be born and grew up healthily when UHRF2 was deleted, and presented little macroscopical difference. Global DNA methylation was normal, but DNA hydroxymethylation was decreased significantly. Both DNA hydroxymethylation and UHRF2 level were high in hippocampus and cortex than in other tissues. To study whether DNA hydroxymethylation and UHRF2 can affect brain development and neurobehavioral function, We performed Open field, Contextual Fear condition and Morris water maze tests, and observed impaired learning and memory in the UHRF2 knockout mice. In summary, UHRF2 affects DNA 5-Methylcytosine hydroxylation and acquisition of murine learning and memory.