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CUG‐initiated FGF‐2 induces chromatin compaction in cultured cardiac myocytes and in vitro *
Author(s) -
Sun Guangping,
Doble Bradley W.,
Sun JianMin,
Fandrich Robert R.,
Florkiewicz Robert,
Kirshenbaum Lorrie,
Davie James R.,
Cattini Peter A.,
Kardami Elissavet
Publication year - 2001
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/1097-4652(2000)9999:999<000::aid-jcp1044>3.0.co;2-2
Subject(s) - chromatin , prophase , mitosis , biology , microbiology and biotechnology , histone , fibroblast growth factor , myocyte , premature chromosome condensation , dna , gene , biochemistry , meiosis , receptor
Fibroblast growth factor‐2 (FGF‐2) is a mitogen found in CUG‐initiated 21–25 kDa (“hi”) or AUG‐initiated 16–18 kDa (“lo”) forms. Previously we demonstrated that “hi”—but not “lo”—FGF‐2 caused a distinct nuclear phenotype characterized by apparently condensed chromatin present as separate clumps in the nucleus of cardiac myocytes. In this manuscript we investigated whether these effects were related to apoptosis or mitosis and whether they reflected 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 positive for TUNEL; (iii) their nuclear lamina, visualized by anti‐laminB immunofluorescence, appeared intact; (iv) neither caspase inhibitors, nor Bcl‐2 or “lo” FGF‐2 overexpression prevented the manifestation of the compacted nuclear phenotype. Purified recombinant “hi” FGF‐2 was more potent than “lo” FGF‐2 in promoting the condensation/aggregation of chick erythrocyte chromatin partially reconstituted with histone H1 in vitro. We conclude that the DNA phenotype induced by “hi” FGF‐2 in cardiac myocytes likely reflects a direct effect on chromatin structure that does not require the engagement of mitosis or apoptosis. By affecting chromatin compaction “hi” FGF‐2 may contribute to the regulation of gene expression. © 2001 Wiley‐Liss, Inc.