This web page was produced as an assignment forGenetics 677, an undergraduate course in UW Madison
DNA motif search
In order to identify important transcriptional or translational regulators of the GSK3B I used the Motif search database and the nucleotide sequence. The parameters of the search were left at default. Even though the highest score that came from the results detected heat shock factors as major binding proteins, the ones that I found most interesting were NF-ATc, GATA1, GATA2, and GATA3 scores. The data is summarized in the table below.
The reason why I found these factors particularly interesting is that some researchers (et al Kerkela, 2008; et al Hardt, 2002) identified NF-ATc,GATA4, Cylin D1 and c-Myc as major genes involved in cardiac hypertrophy and provide data where the expression of these genes is upregulated in mutants lacking GSK3b gene. According to them normally GSK3B directly phosphorylates these molecules and causes their nuclear export and therefore inhibiting transcription of certain genes, some of which are involved in cardiac hypertrophy. Even though only NF-ATc was the only one from the above list, suggested by the database to have some influence on the GSK3B expression, GATA family transcription factors also might be interesting to investigate.
I looked in the GEO database for available microarray data and the only protein (from GATA1,2,3,4; NF-ATc; c-Myc; Cyclin D1) that I was able to find was the GATA1 factor. However the results were ambiguous – for the same experiment performed in macrophages two different reporter detected either upregulation or downregulation of the GSK3B upon GATA1 knock down.(Figure 1 and 2).
I looked in the GEO database for available microarray data and the only protein (from GATA1,2,3,4; NF-ATc; c-Myc; Cyclin D1) that I was able to find was the GATA1 factor. However the results were ambiguous – for the same experiment performed in macrophages two different reporter detected either upregulation or downregulation of the GSK3B upon GATA1 knock down.(Figure 1 and 2).
Figure 1
Figure 2
Title: GDS1245 / 1437001_at / Gsk3b / Mus musculus
Summary: Analysis of megakaryocytes lacking the transcription factor GATA-1. GATA-1 is required for the development of megakaryocytes and erythroid cells. Megakaryocytes obtained from 13.5 day C57BL/6 mutant embryos. Results provide insight into the role of GATA-1 in megakaryopoiesis.
Retrieved from GEO website: http://www.ncbi.nlm.nih.gov/geo/
Summary: Analysis of megakaryocytes lacking the transcription factor GATA-1. GATA-1 is required for the development of megakaryocytes and erythroid cells. Megakaryocytes obtained from 13.5 day C57BL/6 mutant embryos. Results provide insight into the role of GATA-1 in megakaryopoiesis.
Retrieved from GEO website: http://www.ncbi.nlm.nih.gov/geo/
Title: GDS1245 / 1439949_at / Gsk3b / Mus musculus
Summary: Analysis of megakaryocytes lacking the transcription factor GATA-1. GATA-1 is required for the development of megakaryocytes and erythroid cells. Megakaryocytes obtained from 13.5 day C57BL/6 mutant embryos. Results provide insight into the role of GATA-1 in megakaryopoiesis.
Retrieved from GEO website: http://www.ncbi.nlm.nih.gov/geo/
Summary: Analysis of megakaryocytes lacking the transcription factor GATA-1. GATA-1 is required for the development of megakaryocytes and erythroid cells. Megakaryocytes obtained from 13.5 day C57BL/6 mutant embryos. Results provide insight into the role of GATA-1 in megakaryopoiesis.
Retrieved from GEO website: http://www.ncbi.nlm.nih.gov/geo/
Analysis: It is obvious that there is not much microarray research done to investigate relationships between gene expression of GSK3B and the proteins regulators of cardiac hypertrophy. This might be an interesting field that could be further investigated.
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References
1.Motif search: http://motif.genome.jp/
2. GEO database: http://www.ncbi.nlm.nih.gov/geo/
3.Kerkela, R. (2008). Deletion of GSK-3 beta in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation. The journal of clinical investigation, 118, iss:11, 3609 -3618
4. Hardt, S. (2002). Glycogen synthase kinase – 3beta a novel regulatorof cardiac hypertrophy and development..Journal of the American heart association, 90, 1055-1063
2. GEO database: http://www.ncbi.nlm.nih.gov/geo/
3.Kerkela, R. (2008). Deletion of GSK-3 beta in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation. The journal of clinical investigation, 118, iss:11, 3609 -3618
4. Hardt, S. (2002). Glycogen synthase kinase – 3beta a novel regulatorof cardiac hypertrophy and development..Journal of the American heart association, 90, 1055-1063
