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PLoS One. 2013;8(1):e51436. doi: 10.1371/journal.pone.0051436. Epub 2013 Jan 17.

An epigenetic feedback regulatory loop involving microRNA-195 and MBD1 governs neural stem cell differentiation.

Author information

1
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.

Abstract

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).

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.

CONCLUSIONS/SIGNIFICANCE:

Therefore the regulatory loop formed by MBD1 and miR-195 is an important component of the epigenetic network that controls aNSC fate.

PMID:
23349673
PMCID:
PMC3547917
DOI:
10.1371/journal.pone.0051436
[Indexed for MEDLINE]
Free PMC Article

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