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


RESULTS
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
Therefore the regulatory loop formed by MBD1 and miR-195 is an important component of the epigenetic network that controls aNSC fate.
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.
Changmei
C
Liu
Zhao-Qian
ZQ
Teng
Andrea L
AL
McQuate
Emily M
EM
Jobe
Christa C
CC
Christ
Sergei J
SJ
von Hoyningen-Huene
Marie D
MD
Reyes
Eric D
ED
Polich
Yina
Y
Xing
Yue
Y
Li
Weixiang
W
Guo
Xinyu
X
Zhao
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D018891:Dentate Gyrus / Q000166:cytology; D044127:Epigenesis, Genetic; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000235:genetics; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C569389:MIRN195a microRNA, mouse; C489323:Mbd1 protein, mouse; D035683:MicroRNAs