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Cell transformation by c-Ha-rasVal12 oncogene is accompanied by a decrease in histone H1° and an increase in nucleosomal repeat length
Jens Laitinen,
Lea Sistonen,
Kari Alitalo,
Erkki Hölttä,
Corresponding Author
Jens Laitinen
Department of Pathology, University of Helsinki, FIN-00014 Helsinki, Finland
Department of Pathology, University of Helsinki, P.O. Box 21, (Haartmaninkaty 3). FIN-00014 Helsinki, FinlandSearch for more papers by this authorLea Sistonen
Department of Pathology, University of Helsinki, FIN-00014 Helsinki, Finland
Search for more papers by this authorKari Alitalo
Department of Pathology, University of Helsinki, FIN-00014 Helsinki, Finland
Search for more papers by this authorErkki Hölttä
Department of Pathology, University of Helsinki, FIN-00014 Helsinki, Finland
Search for more papers by this authorJens Laitinen,
Lea Sistonen,
Kari Alitalo,
Erkki Hölttä,
Corresponding Author
Jens Laitinen
Department of Pathology, University of Helsinki, FIN-00014 Helsinki, Finland
Department of Pathology, University of Helsinki, P.O. Box 21, (Haartmaninkaty 3). FIN-00014 Helsinki, FinlandSearch for more papers by this authorLea Sistonen
Department of Pathology, University of Helsinki, FIN-00014 Helsinki, Finland
Search for more papers by this authorKari Alitalo
Department of Pathology, University of Helsinki, FIN-00014 Helsinki, Finland
Search for more papers by this authorErkki Hölttä
Department of Pathology, University of Helsinki, FIN-00014 Helsinki, Finland
Search for more papers by this authorAbstract
The activated c-Ha-rasVal12 oncogene is often involved in the genesis of human malignancies. We show here that in c-Ha-rasVal12 oncogene-transformed mouse NIH 3T3 fibroblasts the copy number and expression level of the mutant ras oncogene correlates with the degree of chromatin decondensation, as assessed by micrococcal nuclease (MNase) and DNase I digestion. MNase and DNase I analyses further revealed that the nucleosomal repeat lengths were different in the normal and ras oncogene-transformed cells, 162.3 bp and 178.1 bp, respectively. These chromatin changes were accompanied by alterations in the content of histone H1°. Furthermore, using DNase I as a probe, we discovered that serum stimulation of normal and transformed cells, synchronized by serum starvation, induces rapid reversible changes in the structure of bulk chromatin that may be linked to transcriptional activation. Our data thus indicate that cell transformation by ras is associated with specific changes in chromatin structure that make it more vulnerable, and prone to additional mutations characteristic of cancer development in vivo.
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