Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Novel repressor of the human FMR1 gene - Identification of p56 human (GCC)n-binding protein as a Krüppel-like transcription factor ZF5. / Orlov, Sergey V.; Kuteykin-Teplyakov, Konstantin B.; Ignatovich, Irina A.; Dizhe, Ella B.; Mirgorodskaya, Olga A.; Grishin, Alexander V.; Guzhova, Olga B.; Prokhortchouk, Egor B.; Guliy, Pavel V.; Perevozchikov, Andrej P.
в: FEBS Journal, Том 274, № 18, 09.2007, стр. 4848-4862.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Novel repressor of the human FMR1 gene - Identification of p56 human (GCC)n-binding protein as a Krüppel-like transcription factor ZF5
AU - Orlov, Sergey V.
AU - Kuteykin-Teplyakov, Konstantin B.
AU - Ignatovich, Irina A.
AU - Dizhe, Ella B.
AU - Mirgorodskaya, Olga A.
AU - Grishin, Alexander V.
AU - Guzhova, Olga B.
AU - Prokhortchouk, Egor B.
AU - Guliy, Pavel V.
AU - Perevozchikov, Andrej P.
PY - 2007/9
Y1 - 2007/9
N2 - A series of relatively short (GCC)n triplet repeats (n = 3-30) located within regulatory regions of many mammalian genes may be considered as putative cis-acting transcriptional elements (GCC-elements). Fragile X-mental retardation syndrome is caused by an expansion of (GCC)n triplet repeats within the 5′-untranslated region of the human fragile X-mental retardation 1 (FMR1) gene. The present study aimed to characterize a novel human (GCC)n-binding protein and investigate its possible role in the regulation of the FMR1 gene. A novel human (GCC)n-binding protein, p56, was isolated and identified as a Krüppel-like transcription factor, ZF5, by MALDI-TOF analysis. The capacity of ZF5 to specifically interact with (GCC)n triplet repeats was confirmed by the electrophoretic mobility shift assay with purified recombinant ZF5 protein. In cotransfection experiments, ZF5 overexpression repressed activity of the GCC-element containing mouse ribosomal protein L32 gene promoter. Moreover, RNA interference assay results showed that endogenous ZF5 acts as a repressor of the human FMR1 gene. Thus, these data identify a new class of ZF5 targets, a subset of genes containing GCC-elements in their regulatory regions, and raise the question of whether transcription factor ZF5 is implicated in the pathogenesis of fragile X syndrome.
AB - A series of relatively short (GCC)n triplet repeats (n = 3-30) located within regulatory regions of many mammalian genes may be considered as putative cis-acting transcriptional elements (GCC-elements). Fragile X-mental retardation syndrome is caused by an expansion of (GCC)n triplet repeats within the 5′-untranslated region of the human fragile X-mental retardation 1 (FMR1) gene. The present study aimed to characterize a novel human (GCC)n-binding protein and investigate its possible role in the regulation of the FMR1 gene. A novel human (GCC)n-binding protein, p56, was isolated and identified as a Krüppel-like transcription factor, ZF5, by MALDI-TOF analysis. The capacity of ZF5 to specifically interact with (GCC)n triplet repeats was confirmed by the electrophoretic mobility shift assay with purified recombinant ZF5 protein. In cotransfection experiments, ZF5 overexpression repressed activity of the GCC-element containing mouse ribosomal protein L32 gene promoter. Moreover, RNA interference assay results showed that endogenous ZF5 acts as a repressor of the human FMR1 gene. Thus, these data identify a new class of ZF5 targets, a subset of genes containing GCC-elements in their regulatory regions, and raise the question of whether transcription factor ZF5 is implicated in the pathogenesis of fragile X syndrome.
KW - (GCC)
KW - FMR1
KW - Fragile X syndrome
KW - Triplet repeats
KW - ZF5
KW - Zinc finger transcription factors
UR - http://www.scopus.com/inward/record.url?scp=34548402660&partnerID=8YFLogxK
U2 - 10.1111/j.1742-4658.2007.06006.x
DO - 10.1111/j.1742-4658.2007.06006.x
M3 - Article
C2 - 17714511
AN - SCOPUS:34548402660
VL - 274
SP - 4848
EP - 4862
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 18
ER -
ID: 91966383