Δομή της χρωματίνης και γονιδιακή έκφραση: μοριακοί μηχανισμοί έκφρασης του γονιδίου της ιντερφερόνης Β

Abstract

HMGI/Y plays an important role in the transcriptional control of many genes, although is not a transcription factor. It binds to the minor groove of DNA and helps the synergistic binding of the transcription factors. This can lead to the formation of a very stable complex, termed enhanceosome and results to very high levels of transcription. The last years the role of HMGI/Y in gene expression and tumorigenesis is being elucidated. Although the role of intergenic and intronic regions is very important in transcription regulation no laboratory has ever examined the binding sites of HMGI/Y in these regions. We overexpressed the HMGI/Y protein (myc tagged) in MCF-7 human adenocarcinoma breast cell line. The HMGI/Y overexpression transforms these cells to metastatic. We immunoprecipitate the DNA binding sites of the protein and after digestion with a restriction enzyme (4-cutter) the fragments are ligated to pKSII plasmid with compatible ends. After sequencing and blasting we are able to determine the exact position of these fragments in the human genome. Although the number of the unique sites is relatively small (234) we can see, for the first time, some important details. 84% of the sites are correlated with genes implicated in tumorigenesis and 15% especially with breast tumorigenesis. 44% is in intronic regions and the rest in intergenic regions. This finding underlines the role of the introns in the transcriptional regulation. Chromosome 5 that contains