Nuclear chromatin changes during post-natal myocardial development.
The proliferative capacity of rat myocardium declines rapidly during the first few weeks of post-natal life. In order to gain insight into the mechanisms involved in this decline, we studied the structure and function of nuclear chromatin from isolated rat myocardial cells during post-natal growth. Chromatin template activity decreased progressively (7.5 +/- 0.3 pmol [3H]UTP/microgram DNA per min at age 5 days compared to 2.2 +/- 0.1 pmol [3H]UTP/microgram DNA per min at age 6 months) and was associated with a decrease in the number of transcription initiation sites. This decline was accompanied by changes in chromatin structure as evidenced by: (a) decreased susceptibility to DNAase I digestion with advancing age, (b) decreased poly-L-lysine binding (60% decrease between day 5 and six months of age), (c) progressive decline in positive ellipticity of circular dichroism spectra between 250--300 nm, and (d) derivative melting profiles showing a decrease in DNA regions bound by non-histone proteins and concomitant increase in histone-bound regions. The protein composition of myocardial chromatin also changed during post-natal development, chiefly due to a progressive increase in the histone/DNA ratio. These results indicate substantial changes in the organization and functional capacity of myocardial chromatin during early post-natal growth. These changes accompany, and may contribute to, the restriction in the proliferative capacity of myocardial cells.
D000375:Aging; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism; D006321:Heart / Q000254:growth & development*; D006657:Histones / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D013698:Templates, Genetic; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; D012313:RNA; D004247:DNA