Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation

By Changmei Liu, Zhao‐Qian Teng, Nicholas J. Santistevan, Keith E. Szulwach, Weixiang Guo, Peng Jin, Xinyu Zhao. 2010

324 citations recorded by the source corpus.

Summary Methyl-CpG binding protein 1 (MBD1) regulates gene expression via a DNA methylation-mediated epigenetic mechanism. We have previously demonstrated that MBD1 deficiency impairs adult neural stem/progenitor cell (aNSC) differentiation and neurogenesis, but the underlying mechanism was unclear. Here we show that MBD1 regulates the expression of several microRNAs in aNSCs, and specifically that miR-184 is directly repressed by MBD1. High levels of miR-184 promoted proliferation but inhibited differentiation of aNSCs, whereas inhibition of miR-184 rescued the phenotypes associated with MBD1 deficiency. We further found that miR-184 regulates the expression of Numblike (Numbl), a known regulator of brain development, by binding to the 3′-UTR of Numbl mRNA and affecting its translation. Expression of exogenous Numbl could rescue the aNSC defects that result from either miR-184 overexpression or MBD1 deficiency. Therefore MBD1, miR-184, and Numbl form a regulatory network that helps control the balance between proliferation and differentiation of aNSCs.

Subfields: Cancer Research, Developmental Neuroscience, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Hongjun Song
2. Guo-li Ming
3. Fred H. Gage

In Developmental Neuroscience

1. Hongjun Song
2. Guo-li Ming
3. Fred H. Gage
4. Junjie U. Guo
5. M. Marchetto
6. James Bradley Aimone
7. Wei Deng
8. Chunmei Zhao

In Molecular Biology

1. Hongjun Song
2. Guo-li Ming
3. Fred H. Gage
4. M. Marchetto
5. Jiawei Sun
6. Jiaqi Sun
7. German Ignacio Parisi

Citations in the corpus

• Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “For example, Methyl-CpG-binding domain protein 1 (Mbd1) suppresses the expression of FGF-2 and several miRNAs to control the balance between proliferation and differentiation during adult hippocampal neurogenesis (Liu et al., 2010).”
• The role of adult hippocampal neurogenesis in brain health and disease (2018, unknown): “Epigenetic modifiers Type1, 2a and 2b Proliferation of RGLs/NPs GADD45b [244], TET1 [245], miR-137 [246], miR-17-92 [247], Nup153 [248] Differentiation of RGLs/NPs MBD1 [249–252], HDAC1 [173, 204], HDAC2 [253], MeCP2 [173, 246, 254–256], miR-184 [250], miR-199 [256]”
• Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning (2011, unknown): “We maintained aNSCs and carried out cell proliferation and differentiation analyses as previously describe”
• Epigenetic choreographers of neurogenesis in the adult mammalian brain (2010, background): “First, miR-184 functions as a direct target of Mbd1 to inhibit neuronal differentiation from adult neural stem cells in the SG”
• Epigenetic regulation of neurogenesis in the adult mammalian brain (2011, background): “1B, and see below; Liu et al., 2010).”