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. 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. Conclusion- 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.
| Original language | English |
|---|---|
| Pages (from-to) | 898-907 |
| Number of pages | 10 |
| Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Volume | 31 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2011 |
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Keywords
- biology developmental
- differentiation
- epigenetics
- gene expression
- microRNA
- molecular biology
- nitric oxide
- vascular biology
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Smad-interacting protein-1 and microRNA 200 family define a nitric oxide-dependent molecular circuitry involved in embryonic stem cell mesendoderm differentiation. / Rosati, Jessica; Spallotta, Francesco; Nanni, Simona; Grasselli, Annalisa; Antonini, Annalisa; Vincenti, Sara; Presutti, Carlo; Colussi, Claudia; D'Angelo, Carmen; Biroccio, Anna; Farsetti, Antonella; Capogrossi, Maurizio C.; Illi, Barbara; Gaetano, Carlo.
In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 31, No. 4, 04.2011, p. 898-907.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Smad-interacting protein-1 and microRNA 200 family define a nitric oxide-dependent molecular circuitry involved in embryonic stem cell mesendoderm differentiation
AU - Rosati, Jessica
AU - Spallotta, Francesco
AU - Nanni, Simona
AU - Grasselli, Annalisa
AU - Antonini, Annalisa
AU - Vincenti, Sara
AU - Presutti, Carlo
AU - Colussi, Claudia
AU - D'Angelo, Carmen
AU - Biroccio, Anna
AU - Farsetti, Antonella
AU - Capogrossi, Maurizio C.
AU - Illi, Barbara
AU - Gaetano, Carlo
PY - 2011/4
Y1 - 2011/4
N2 - 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. 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. Conclusion- 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.
AB - 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. 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. Conclusion- 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.
KW - biology developmental
KW - differentiation
KW - epigenetics
KW - gene expression
KW - microRNA
KW - molecular biology
KW - nitric oxide
KW - vascular biology
UR - http://www.scopus.com/inward/record.url?scp=79953744099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953744099&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.110.214478
DO - 10.1161/ATVBAHA.110.214478
M3 - Article
C2 - 21233447
AN - SCOPUS:79953744099
VL - 31
SP - 898
EP - 907
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 4
ER -