Bre1, a histone 2B ubiquitin ligase, is one of the modulators of neural stem cell fate
演題番号 : P1-d19
石野 雄吾 / Yugo Ishino:1,2 Akhilesh Kumar:2 成瀬 雅衣 / Masae Naruse:2 等 誠司 / Seiji Hitoshi:1,2 池中 一裕 / Kazuhiro Ikenaka:1,2
1:総研大・生命・生理 / Dept Physiol Sci, SOKENDAI, Hayama 2:生理研・分子神経 / Div Neurobio Bioinfo, NIPS, Okazaki
Neural stem cells have the capacity to self-renew and multipotency to give rise to neurons, astrocytes and oligodendrocytes. However, it is unclear how those un-differentiated and differentiated states are determined. There are increasing evidences that epigenetic mechanisms, such as DNA methylation, histone modification and non-coding RNA expression, play important roles in controlling stem cell self-renewal and differentiation.
We focused on E3 monoubiqutin ligase Bre1, whose target is histone 2B(H2B) protein. The H2B monoubiquitination leads to the change in the genome structure, which affects gene expression. We hypothesized that this histone modification changes expression of the genes essential for neural stem cell fate specification.
Bre1 is strongly expressed in the ventricular and subventricular zones at the embryonic stage, and around the lateral ventricle in the adult brain in mouse, where neural stem or progenitor cells exist. This suggests that Bre1 plays some roles in these cells.
To investigate Bre1 function in neural stem cells, we analyzed its role in the developing neocortex by gain-of-function approaches using in utero electroporation. Bre1 overexpressing cells showed migration defects indicating that Bre1 modified cell fate. We are analyzing whether Bre1 overexpressing cells have changed their cell fates, and investigating the influence of Bre1 overexpression at the several developing stages.