Chromatin reorganization during emergence of malignant Friend tumors: early changes in H2A and H2B variants and nucleosome repeat length.

Serial examination of five newly derived Friend murine tumors during early subcutaneous passages showed continuing changes in chromatin composition and structure over the first 10 to 20 passages followed by a period of stabilization over the subsequent 20 passages. These changes were reflected in a decrease in two major histone variants, H2A.1 and H2B.2, with a coordinate increase in histone variants, H2A.2 and H2B.1, and a changing nucleosome repeat length (NRL). The absolute values differed among the five tumors, but all five showed the same general direction of change. There was no obvious relationship among the NRL, H2A, and H2B histone variant values. A low H2A.1/H2A.2 ratio was found in Friend tumors of high malignant potential. Cell lines derived in vitro also showed directional changes in the H2A and H2B variants similar to those of their tumor cell parents, but with different kinetics. Our findings suggest that Friend tumor establishment is accompanied by an early period of chromatin reorganization marked by changes in several parameters of chromatin structure.