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Smad-interacting protein-1 and microRNA 200 family define a nitric oxide-dependent molecular circuitry involved in embryonic stem cell mesendoderm differentiation.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2011 Apr; Vol. 31 (4), pp. 898-907. Date of Electronic Publication: 2011 Jan 13. - Publication Year :
- 2011
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Abstract
- Objective: Smad-interacting protein-1 (Sip1/ZEB2) is a transcriptional repressor of the telomerase reverse transcriptase catalytic subunit (Tert) and has recently been identified as a key regulator of embryonic cell fate with a phenotypic effect similar, in our opinion, to that reported for nitric oxide (NO). Remarkably, SIP1/ZEB2 is a known target of the microRNA 200 (miR-200) family. In this light, we postulated that Sip1/ZEB2 and the miR-200 family could play a role during the NO-dependent differentiation of mES.<br />Methods and Results: The results of the present study show that Sip1/ZEB2 expression is downregulated during the NO-dependent expression of mesendoderm and early cardiovascular precursor markers, including Flk1 and CXCR4 in mES. Coincidently, members of the miR-200 family, namely miR-429, -200a, -200b, and -200c, were transcriptionally induced in parallel to mouse Tert. This regulation occurred at the level of chromatin. Remarkably, miR-429/miR-200a overexpression or Sip1/ZEB2 knockdown by short hairpin RNA interference elicited a gene expression pattern similar to that of NO regardless of the presence of leukemia inhibitory factor.<br />Conclusions: These results are the first demonstrating that the miR-200 family and Sip1/ZEB2 transcription factor are regulated by NO, indicating an unprecedented molecular circuitry important for telomerase regulation and early differentiation of mES.
- Subjects :
- Animals
Cells, Cultured
Chromatin Assembly and Disassembly
Embryonic Stem Cells drug effects
Gene Expression Regulation, Developmental
Homeodomain Proteins genetics
Leukemia Inhibitory Factor metabolism
Mice
Nitric Oxide Donors pharmacology
RNA Interference
RNA, Messenger metabolism
Repressor Proteins genetics
Telomerase metabolism
Time Factors
Transcription, Genetic
Transfection
Zinc Finger E-box Binding Homeobox 2
Cell Differentiation drug effects
Embryonic Stem Cells metabolism
Homeodomain Proteins metabolism
MicroRNAs metabolism
Nitric Oxide metabolism
Repressor Proteins metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 31
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 21233447
- Full Text :
- https://doi.org/10.1161/ATVBAHA.110.214478