Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression
Abstract
The expression of Sox14 gene in spinal cord explants was found to be regulated by Sonic hedgehog (SHH) in a dose-dependent manner, indicating that this signaling molecule might act as a regulator of Sox14-expressing interneuron differentiation. In the present study we identified the positive control element and provided the first evidence that FOXA2 is involved in up-regulation of SOX14 expression in HepG2 and U87MG cell lines. By functional analysis we demonstrated that mutation in FOXA2 binding site reduced the SOX14 reporter construct activity, and that FOXA2 over-expression increased endogenous SOX14 protein expression. Further, we have shown that human SOX14 expression is GLI1 dependent in U87MG cells and SHH-N dependent in U87MG and HepG2 cell lines. By applying siRNA silencing of FOXA2, we have demonstrated that upregulation of endogenous SOX14 gene expression by SHH is, at least in part, mediated by FOXA2. However, our data revealed that a positive regulatory region, containing... functional FOXA2 site analyzed in this study, is not involved in mediation of SHH dependent SOX14 activation. Data presented here provide the initial insight into molecular mechanism underlying tissue and developmentally specific regulation of the SOX14 gene expression.
Keywords:
SOX14 / SHH / GU / Foxa2Source:
Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms, 2010, 1799, 5-6, 411-418Publisher:
- Elsevier Science Bv, Amsterdam
Funding / projects:
- Izučavanje regulacije ekspresije i funkcije humanih SOX gena (RS-MESTD-MPN2006-2010-143028)
DOI: 10.1016/j.bbagrm.2010.01.002
ISSN: 1874-9399
PubMed: 20074681
WoS: 000278321400006
Scopus: 2-s2.0-77953697683
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Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Popović, Jelena AU - Lazić, Andrijana AU - Petrović, Isidora AU - Stevanović, Milena PY - 2010 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/430 AB - The expression of Sox14 gene in spinal cord explants was found to be regulated by Sonic hedgehog (SHH) in a dose-dependent manner, indicating that this signaling molecule might act as a regulator of Sox14-expressing interneuron differentiation. In the present study we identified the positive control element and provided the first evidence that FOXA2 is involved in up-regulation of SOX14 expression in HepG2 and U87MG cell lines. By functional analysis we demonstrated that mutation in FOXA2 binding site reduced the SOX14 reporter construct activity, and that FOXA2 over-expression increased endogenous SOX14 protein expression. Further, we have shown that human SOX14 expression is GLI1 dependent in U87MG cells and SHH-N dependent in U87MG and HepG2 cell lines. By applying siRNA silencing of FOXA2, we have demonstrated that upregulation of endogenous SOX14 gene expression by SHH is, at least in part, mediated by FOXA2. However, our data revealed that a positive regulatory region, containing functional FOXA2 site analyzed in this study, is not involved in mediation of SHH dependent SOX14 activation. Data presented here provide the initial insight into molecular mechanism underlying tissue and developmentally specific regulation of the SOX14 gene expression. PB - Elsevier Science Bv, Amsterdam T2 - Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms T1 - Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression EP - 418 IS - 5-6 SP - 411 VL - 1799 DO - 10.1016/j.bbagrm.2010.01.002 ER -
@article{ author = "Popović, Jelena and Lazić, Andrijana and Petrović, Isidora and Stevanović, Milena", year = "2010", abstract = "The expression of Sox14 gene in spinal cord explants was found to be regulated by Sonic hedgehog (SHH) in a dose-dependent manner, indicating that this signaling molecule might act as a regulator of Sox14-expressing interneuron differentiation. In the present study we identified the positive control element and provided the first evidence that FOXA2 is involved in up-regulation of SOX14 expression in HepG2 and U87MG cell lines. By functional analysis we demonstrated that mutation in FOXA2 binding site reduced the SOX14 reporter construct activity, and that FOXA2 over-expression increased endogenous SOX14 protein expression. Further, we have shown that human SOX14 expression is GLI1 dependent in U87MG cells and SHH-N dependent in U87MG and HepG2 cell lines. By applying siRNA silencing of FOXA2, we have demonstrated that upregulation of endogenous SOX14 gene expression by SHH is, at least in part, mediated by FOXA2. However, our data revealed that a positive regulatory region, containing functional FOXA2 site analyzed in this study, is not involved in mediation of SHH dependent SOX14 activation. Data presented here provide the initial insight into molecular mechanism underlying tissue and developmentally specific regulation of the SOX14 gene expression.", publisher = "Elsevier Science Bv, Amsterdam", journal = "Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms", title = "Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression", pages = "418-411", number = "5-6", volume = "1799", doi = "10.1016/j.bbagrm.2010.01.002" }
Popović, J., Lazić, A., Petrović, I.,& Stevanović, M.. (2010). Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression. in Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms Elsevier Science Bv, Amsterdam., 1799(5-6), 411-418. https://doi.org/10.1016/j.bbagrm.2010.01.002
Popović J, Lazić A, Petrović I, Stevanović M. Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression. in Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms. 2010;1799(5-6):411-418. doi:10.1016/j.bbagrm.2010.01.002 .
Popović, Jelena, Lazić, Andrijana, Petrović, Isidora, Stevanović, Milena, "Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression" in Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms, 1799, no. 5-6 (2010):411-418, https://doi.org/10.1016/j.bbagrm.2010.01.002 . .