2000 Fiscal Year Final Research Report Summary
Transcriptional coactivator UTF1 as an embryonic stem cell cofactor for retinoic acid receptor
| Project/Area Number |
11670133
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Saitama Medical School |
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Principal Investigator |
OKUDA Akihiko Saitama Medical School Biochemistry Associate Professor, 医学部, 講師 (60201993)
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| Co-Investigator(Kenkyū-buntansha) |
ORIMO Akira Saitama Medical School Biochemistry Assistant Professor, 医学部, 助手 (70275866)
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| Project Period (FY) |
1999 – 2000
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| Keywords | mammal / early embryogenesis / embryonic carcinoma / retinoic acid / transcriptional cofactor |
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| Research Abstract |
Embryonic carcinoma (EC) cell lines such as F9 and P19 cells are widely used as a model system for studying the molecular basis governing early developmental stages of mammals. The EC cells possess a number of properties which resemble those of early embryonic cells. For example, these EC cells retain pluripotent properties and can be induced to differentiate into several types of cells such as muscle and nerve cells using retinoic acid and/or by aggregate formation. Early studies carried out in EC cells clearly indicated that these cells have a number of interesting and unique regulatory features. One of such examples is that about the regulation of retinoic acid receptor (RAR) β2 gene expression. The promoter of this gene carries two RAR responsive element (RARE) and its activity is autoregulated by its own gene. However, it has been demonstrated that the gene requires an additional embryonic stem cell cofactor for its expression..
In 1998, I have molecularly cloned a novel transcript
… More
ional coactivator UTF1 whose expression is restricted to early embryonic cells. When I looked the amino acid sequence carefully, I found that the protein contains two LxxLL motif in the one of the evolutionarily conserved domain which is commonly present in nuclear receptor cofactor such as SRC-1 and TIF-2 and is demonstrated to be involved in the interaction with nuclear receptor. Therefore, I hypothesized that the UTF1 may correspond to the embyonic stem cell specific cofactor required for RARβ2 gene expression. By the transient transfection, I demonstrated that UTF1 is able to stimulate transcription from this promoter. Furthermore, I found that this activation of transcription is occurred through the RARE.I also demonstrated, by GST pull down assay, that UTF1 is able to bind to RAR directly. However, this interaction is found to be independent of retinoic acid and AF2 domain of the RAR.Thus, the UTF1 appears to bind to RAR in a distinct way from other nuclear receptor cofactors such as SRC-1 and TIF-2. Less
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[Publications] Yogosawa, S., Kayuyama, K., Inoue, S., Okuda, A., Muramatsu, M., and Tamura, T.: "Induced expression, localization, and chromosome mapping of a gene for the TBP-interacting protein 120A."Biochem.Biophy.Res.Commun.. 266. 123-128 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Orimo, A., Inoue, S., Minowa, O., Tominaga, N., Sato, M., Kuno, J., Hiroi, H., Shimizu, Y., Suzuki, M., Noda, T., and Muramatsu, M.: "Undeveloped uterus and reduced estrogen responsiveness in mice with dsruption of the estrogen-responsive finger protein gene, which is a direct target of estroge receptor alpha."Proc.Natl.Acad.Sci.USA. 96. 12027-12032 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Ogawa, S., Fujita, M., Ishii, Y., Tsurukami, H., Hirabayashi, M., Ikeda, K., Orimo, A., Hosoi, T., Ueda, M., Nakamura, T., Ouchi, Y., Muramatsu, M., and Inoue, S.: "Impaired estrogen sensitivity in bone by inhibiting both estrogen receptor alpha and beta pathways."J.Biol.Chem.. 275. 21372-21379 (2000)
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「研究成果報告書概要(欧文)」より
