CUC-initiated FCF-2 induces chromatin compaction in cultured cardiac myocytes and in vitro

Fibroblast growth factor-2 (FGF-2) is a mitogen found in CUC-initiated 21-2 5 kDa ("hi") or AUG-initiated 16-18 kDa ("lo") forms. Previously we demonst rated that "hi"-but not "lo"-FGF-2 caused a distinct nuclear phenotype char acterized by apparently condensed chromatin present as separate clumps in t he nucleus of cardiac myocytes. In this manuscript we investigated whether these effects were related to apoptosis or mitosis and whether they reflect ed a direct effect of "hi" FGF-2 on chromatin. Myocytes overexpressing "hi" FGF-2 and presenting the clumped chromatin phenotype: (i) were not labeled above background with antibodies to phosphorylated histones H1 and H3 used as indicators of mitotic chromatin condensation; (ii) did not stain positi ve for TUNEL; (iii) their nuclear lamina, visualized by anti-laminB immunof luorescence, appeared intact; (iv) neither caspase inhibitors, nor Bcl-2 or "lo" FGF-2 overexpression prevented the manifestation of the compacted nuc lear phenotype. Purified recombinant "hi" FGF-2 was more potent than "lo" F GF-2 in promoting the condensation/aggregation of chick erythrocyte chromat in partially reconstituted with histone H1 in vitro. We conclude that the D NA phenotype induced by "hi" FGF-2 in cardiac myocytes likely reflects a di rect effect on chromatin structure that does not require the engagement of mitosis or apoptosis. By affecting chromatin compaction "hi" FGF-2 may cont ribute to the regulation of gene expression. (C) 2001 Wiley-Liss, Inc.