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Systematically dissecting the global mechanism of miRNA functions in mouse pluripotent stem cells.

Wang A, He Q, Zhong Y - BMC Genomics (2015)

Bottom Line: The decreasing methylation repressed by miRNAs in turn activates the top miRNAs and pluripotent core factors, creating an active circuit system to modulate pluripotency.MiRNAs vary their functions with stem cell states.While miRNAs directly repress pluripotent core factors to facilitate differentiation during the differentiation state, they also help stem cells to maintain pluripotency by activating pluripotent cores through directly repressing DNA methylation systems and primarily inhibiting development in the pluripotent state.

View Article: PubMed Central - PubMed

Affiliation: School of medicine, University of California San Francisco, S-1268, Medical Sciences Building, 513 Parnassus Ave, San Francisco, CA, 94143, USA. anyou.wang@alumni.ucr.edu.

ABSTRACT

Background: MicroRNAs (miRNAs) critically modulate stem cell properties like pluripotency, but the fundamental mechanism remains largely unknown.

Method: This study systematically analyzes multiple-omics data and builds a systems physical network including genome-wide interactions between miRNAs and their targets to reveal the systems mechanism of miRNA functions in mouse pluripotent stem cells.

Results: Globally, miRNAs directly repress the pluripotent core factors during differentiation state. Surprisingly, during the pluripotent state, the top important miRNAs do not directly regulate the pluripotent core factors as previously thought, but they only directly target the pluripotent signal pathways and directly repress developmental processes. Furthermore, at the pluripotent state miRNAs predominately repress DNA methyltransferases, the core enzymes for DNA methylation. The decreasing methylation repressed by miRNAs in turn activates the top miRNAs and pluripotent core factors, creating an active circuit system to modulate pluripotency.

Conclusion: MiRNAs vary their functions with stem cell states. While miRNAs directly repress pluripotent core factors to facilitate differentiation during the differentiation state, they also help stem cells to maintain pluripotency by activating pluripotent cores through directly repressing DNA methylation systems and primarily inhibiting development in the pluripotent state.

No MeSH data available.


MiRNAs directly target a histone complex. The MiR-290-295 cluster heavily attacks the Mef2c
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Fig7: MiRNAs directly target a histone complex. The MiR-290-295 cluster heavily attacks the Mef2c

Mentions: In addition, miRNAs directly and abundantly target a core histone modification complex (Hdac4-Mef2c-Mef2d, http://www.ncbi.nlm.nih.gov/gene/9759) (Fig. 7), including Mef2c (myocyte enhancer factor 2C), which was targeted by the top over-expressed miRNA clusters including miR-290-295 and miR-302 cluster (Fig. 7). Up-regulating Mef2c enhances stem cells differentiation [29], and down-regulated Mef2c inhibits differentiation [29]. The down-regulation of Mef2c targeted by the top over-expressed miRNA clusters suggests that miRNAs repress differentiation in stem cells. This is consistent with our discussion above on the miRNA repressing development and differentiation at the pluripotent state in stem cells (Figs. 2 and 3). Together, miRNAs directly and abundantly target the epigenetic systems at the pluripotent state.Fig. 7


Systematically dissecting the global mechanism of miRNA functions in mouse pluripotent stem cells.

Wang A, He Q, Zhong Y - BMC Genomics (2015)

MiRNAs directly target a histone complex. The MiR-290-295 cluster heavily attacks the Mef2c
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4488055&req=5

Fig7: MiRNAs directly target a histone complex. The MiR-290-295 cluster heavily attacks the Mef2c
Mentions: In addition, miRNAs directly and abundantly target a core histone modification complex (Hdac4-Mef2c-Mef2d, http://www.ncbi.nlm.nih.gov/gene/9759) (Fig. 7), including Mef2c (myocyte enhancer factor 2C), which was targeted by the top over-expressed miRNA clusters including miR-290-295 and miR-302 cluster (Fig. 7). Up-regulating Mef2c enhances stem cells differentiation [29], and down-regulated Mef2c inhibits differentiation [29]. The down-regulation of Mef2c targeted by the top over-expressed miRNA clusters suggests that miRNAs repress differentiation in stem cells. This is consistent with our discussion above on the miRNA repressing development and differentiation at the pluripotent state in stem cells (Figs. 2 and 3). Together, miRNAs directly and abundantly target the epigenetic systems at the pluripotent state.Fig. 7

Bottom Line: The decreasing methylation repressed by miRNAs in turn activates the top miRNAs and pluripotent core factors, creating an active circuit system to modulate pluripotency.MiRNAs vary their functions with stem cell states.While miRNAs directly repress pluripotent core factors to facilitate differentiation during the differentiation state, they also help stem cells to maintain pluripotency by activating pluripotent cores through directly repressing DNA methylation systems and primarily inhibiting development in the pluripotent state.

View Article: PubMed Central - PubMed

Affiliation: School of medicine, University of California San Francisco, S-1268, Medical Sciences Building, 513 Parnassus Ave, San Francisco, CA, 94143, USA. anyou.wang@alumni.ucr.edu.

ABSTRACT

Background: MicroRNAs (miRNAs) critically modulate stem cell properties like pluripotency, but the fundamental mechanism remains largely unknown.

Method: This study systematically analyzes multiple-omics data and builds a systems physical network including genome-wide interactions between miRNAs and their targets to reveal the systems mechanism of miRNA functions in mouse pluripotent stem cells.

Results: Globally, miRNAs directly repress the pluripotent core factors during differentiation state. Surprisingly, during the pluripotent state, the top important miRNAs do not directly regulate the pluripotent core factors as previously thought, but they only directly target the pluripotent signal pathways and directly repress developmental processes. Furthermore, at the pluripotent state miRNAs predominately repress DNA methyltransferases, the core enzymes for DNA methylation. The decreasing methylation repressed by miRNAs in turn activates the top miRNAs and pluripotent core factors, creating an active circuit system to modulate pluripotency.

Conclusion: MiRNAs vary their functions with stem cell states. While miRNAs directly repress pluripotent core factors to facilitate differentiation during the differentiation state, they also help stem cells to maintain pluripotency by activating pluripotent cores through directly repressing DNA methylation systems and primarily inhibiting development in the pluripotent state.

No MeSH data available.