Palomer Ernest, Carretero Javier, Benvegnù Stefano, Dotti Carlos G, Martin Mauricio G
Departamento de Neurobiología Molecular, Centro Biología Molecular 'Severo Ochoa' CSIC-UAM, 28049 Madrid, Spain.
Laboratorio de Neurobiología, Instituto de Investigaciones Médicas Mercedes y Martín Ferreyra (INIMEC-CONICET-UNC), Universidad Nacional de Córdoba, 5016 Córdoba, Argentina.
Nat Commun. 2016 Mar 24;7:11081. doi: 10.1038/ncomms11081.
It has been recently described that in embryonic stem cells, the expression of some important developmentally regulated genes is repressed, but poised for fast activation under the appropriate stimuli. In this work we show that Bdnf promoters are repressed by Polycomb Complex 2 in mature hippocampal neurons, and basal expression is guaranteed by the coexistence with activating histone marks. Neuronal stimulation triggered by N-methyl-D-aspartate application induces the transcription of these promoters by H3K27Me3 demethylation and H3K27Me3 phosphorylation at Serine 28 leading to displacement of EZH2, the catalytic subunit of Polycomb Repressor Complex 2. Our data show that the fast transient expression of Bdnf promoters II and VI after neuronal stimulation is dependent on acetylation of histone H3K27 by CREB-p/CBP. Thus, regulatory mechanisms established during development seem to remain after differentiation controlling genes induced by different stimuli, as would be the case of early memory genes in mature neurons.
最近有研究表明，在胚胎干细胞中，一些重要的发育调控基因的表达受到抑制，但在适当刺激下随时准备快速激活。在这项研究中，我们发现脑源性神经营养因子（Bdnf）启动子在成熟海马神经元中被多梳蛋白复合体2（Polycomb Complex 2）抑制，并且通过与激活组蛋白标记共存来保证基础表达。由N-甲基-D-天冬氨酸（N-methyl-D-aspartate）应用引发的神经元刺激通过H3K27三甲基化（H3K27Me3）去甲基化和丝氨酸28处的H3K27Me3磷酸化诱导这些启动子的转录，导致多梳抑制复合体2的催化亚基EZH2的移位。我们的数据表明，神经元刺激后脑源性神经营养因子启动子II和VI的快速瞬时表达依赖于CREB-p/CBP介导的组蛋白H3K27乙酰化。因此，发育过程中建立的调控机制似乎在分化后仍然存在，控制着由不同刺激诱导的基因，就像成熟神经元中的早期记忆基因一样。
