An Epigenetic Feedback Regulatory Loop Involving MicroRNA-195 and MBD1 Governs Neural Stem Cell Differentiation

作者：Liu Changmei; Teng Zhao Qian; McQuate Andrea L; Jobe Emily M; Christ Christa C; von Hoyningen Huene Sergei J; Reyes Marie D; Polich Eric D; Xing Yina; Li Yue; Guo Weixiang; Zhao Xinyu^*

来源：PLos One, 2013, 8(1): e51436.

DOI：10.1371/journal.pone.0051436

Background: Epigenetic mechanisms, including DNA methylation, histone modification, and microRNAs, play pivotal roles in stem cell biology. Methyl-CpG binding protein 1 (MBD1), an important epigenetic regulator of adult neurogenesis, controls the proliferation and differentiation of adult neural stem/progenitor cells (aNSCs). We recently demonstrated that MBD1 deficiency in aNSCs leads to altered expression of several noncoding microRNAs (miRNAs). %26lt;br%26gt;Methodology/Principal Findings: Here we show that one of these miRNAs, miR-195, and MBD1 form a negative feedback loop. While MBD1 directly represses the expression of miR-195 in aNSCs, high levels of miR-195 in turn repress the expression of MBD1. Both gain-of-function and loss-of-function investigations show that alterations of the MBD1-miR-195 feedback loop tip the balance between aNSC proliferation and differentiation. %26lt;br%26gt;Conclusions/Significance: Therefore the regulatory loop formed by MBD1 and miR-195 is an important component of the epigenetic network that controls aNSC fate.

• 出版日期2013-1-17