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Detection of target genes of FOXA transcription factors involved in proliferation control

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Abstract

To reveal the mechanism of tumor-suppressing activity of FOXA proteins in liver, a search for potential target genes of these transcription factors involved in proliferation control was carried out. In the first step, we have used data from the literature concerning gene expression in mouse liver (high content of FOXA proteins) and kidney (FOXA expression is absent) obtained by hybridization on microchips. A search for FOXA binding sites in regulatory regions of forty differentially expressing genes involved in proliferation control was carried out using the computer method SITECON. Eleven genes containing clusters of potential FOXA sites incorporating 3–6-fold repeats of TTTG were revealed. The FOXA-specific interaction with such microsatellite sites was confirmed by gel-retardation technique using the GST-fused protein containing the DNA-binding domain of FOXA2. Six genes containing clusters of confirmed binding sites—Cul2, Cdc73, Ptk, Pdcd, Creb, and Ppp2r5d—were selected. The effect of hepatocarcinogen orthoaminoazotoluene (OAT), which lowers the FOXA activity, on expression of these genes was studied by the real-time PCR. OAT was shown to increase sharply the level of mRNA of the Cul2 and Cdc73 genes.

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Abbreviations

GST:

glutathione-S-transferase

IPTG:

isopropyl-β-D-thiogalactopyranoside

OAT:

orthoaminoazotoluene

TTR:

transthyretin

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, pr. Akademika Lavrentieva 10, 630090, Novosibirsk, Russia

    L. O. Bryzgalov, N. I. Ershov, D. Yu. Oshchepkov, V. I. Kaledin & T. I. Merkulova

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  1. L. O. Bryzgalov
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  2. N. I. Ershov
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  3. D. Yu. Oshchepkov
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  4. V. I. Kaledin
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  5. T. I. Merkulova
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Correspondence to L. O. Bryzgalov.

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Original Russian Text © L. O. Bryzgalov, N. I. Ershov, D. Yu. Oshchepkov, V. I. Kaledin, T. I. Merkulova, 2008, published in Biokhimiya, 2008, Vol. 73, No. 1, pp. 86–92.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM07-218, November 11, 2007.

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Bryzgalov, L.O., Ershov, N.I., Oshchepkov, D.Y. et al. Detection of target genes of FOXA transcription factors involved in proliferation control. Biochemistry Moscow 73, 70–75 (2008). https://doi.org/10.1134/S0006297908010100

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