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Publication : Transcriptional activation of the cyclin A gene by the architectural transcription factor HMGA2.

First Author  Tessari MA Year  2003
Journal  Mol Cell Biol Volume  23
Issue  24 Pages  9104-16
PubMed ID  14645522 Mgi Jnum  J:175196
Mgi Id  MGI:5284804 Doi  10.1128/MCB.23.24.9104-9116.2003
Citation  Tessari MA, et al. (2003) Transcriptional activation of the cyclin A gene by the architectural transcription factor HMGA2. Mol Cell Biol 23(24):9104-16
abstractText  The HMGA2 protein belongs to the HMGA family of architectural transcription factors, which play an important role in chromatin organization. HMGA proteins are overexpressed in several experimental and human tumors and have been implicated in the process of neoplastic transformation. Hmga2 knockout results in the pygmy phenotype in mice and in a decreased growth rate of embryonic fibroblasts, thus indicating a role for HMGA2 in cell proliferation. Here we show that HMGA2 associates with the E1A-regulated transcriptional repressor p120(E4F), interfering with p120(E4F) binding to the cyclin A promoter. Ectopic expression of HMGA2 results in the activation of the cyclin A promoter and induction of the endogenous cyclin A gene. In addition, chromatin immunoprecipitation experiments show that HMGA2 associates with the cyclin A promoter only when the gene is transcriptionally activated. These data identify the cyclin A gene as a cellular target for HMGA2 and, for the first time, suggest a mechanism for HMGA2-dependent cell cycle regulation.
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