Doctorate Program in Molecular Oncology and Endocrinology

摘要: High mobility group A (HMGA) proteins are chromatinic that do not have transcriptional activity per se, however, by interacting with the transcription machinery, they regulate, negatively or positively, expression of several genes. We searched for genes regulated HMGA1 using microarray analysis in embryonic stem (ES) cells bearing one two disrupted hmga1 alleles. identified 87 transcripts increased and 163 decreased at least 4-fold / ES cells. For some them, a HMGA1-dose dependency was observed, because an intermediate level observed heterozygous When these extended to fibroblasts adult tissues such as heart, spleen, liver from hmga1-knockout mice, contrasting results were obtained. In fact, aside showing same regulation cells, there did modify their expression, others HMGA1mediated but opposite direction. These clearly indicate HMGA1-mediated gene depends on cellular context. Finally couple analyzed HMGA1-regulated genes, electrophoretic shift assay chromatin immunoprecipitation revealed direct binding promoters, suggesting HMGA1-direct expression.