Histone turnover within nonproliferating cells

Abstract

The turnover of DNA and histones in the livers and brains of mice has been determined. These mice had been exposed to constant levels of tritiated water from conception until they were 8 months old. At this point, exposure to tritium was discontinued, and the tritium remaining in DNA and histones was measured at various intervals afterward. The half-lives calculated for these components (with 95% confidence limits given in parentheses) were 117 (85-188) days for liver histone, 318 (241-466) days for liver DNA, It is generally agreed that histone synthesis is closely coupled to DNA synthesis in somatic cells and that the turnover of histones within a tissue is very slow compared to that of other nuclear or cytoplasmic proteins (1, 2). Whether this slow tissue turnover is solely due to cell turnover within the tissue or is in part due to histone turnover within intact cells is at present controversial. Piha et al (3) measured the rate of loss of label from brain and liver histones of mice given '4C-labeled lysine in embryo and concluded that all of the observed histone turnover could be accounted for by cell turnover. On the other hand, Hempel et al (4) measured the rate of incorporation of 3H-labeled methionine into the histones of the adult cat kidney and concluded that histone turnover was rapid and almost entirely due to turnover within the living cell.At the heart ofthis controversy is the magnitude ofcell turnover in these tissues. Piha et aL (3) estimated cell turnover from DNA turnover reported by others. Hempel et al. (4) considered cell turnover in the adult cat kidney to be negligible because very few labeled cells were seen in autoradiographs of these tissues taken after injection of tritiated thymidine. However, values for DNA turnover reported in the literature are not reliable. They are based on relatively few measurements and vary by orders of magnitude. The finding of negligible cell proliferation in adult cat kidneys conflicts with findings of significant incorporation ofDNA precursors in adult mouse kidneys (5) and suggests that the autoradiographic findings might be artifacts.The question ofwhether there is histone turnover within the living cell has important implications relating to the stability of the nucleosome, the basic unit of organization of DNA and histone within the chromosome. Complete lack ofturnover implies that the nucleosome is rigid and inert, whereas significant turnover suggests a flexible, dynamic structure. To help resolve this question, we have determined the rate ofboth histone and DNA turnover in mouse brain and liver. These measurements were made on mice that had been exposed to constant levels of tritiated water from conception until 8 months old. They are based on the rate of loss of tritium from DNA and histones after discontinuing exposure of these mice to tritiated water. MATERIALS AND METHODSThe procedures used here have been described in detail elsewhere (6). Mice were obtained from litters born to parents maintained on tritiated drinking water (3.0 ,AC...

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7

“…These discoveries suggest that the methylated arginines removed from histone tails are neither recycled nor reversed, but rather are completely destroyed through degradation. This result is consistent with the turnover rate of histones in nonproliferating cells (49). JMJD5 has been reported to be critical for the cell cycle (20,21,42).…”

Histone carbonylation in vivo and in vitro

“…It will be interesting to examine the possibility that histone carbonylation increases with tissue age, as has been demonstrated for carbonyl content of total protein in different tissues [31]. The half-life of histones within non-proliferating mouse cells ranges between four and five months, potentially allowing the accumulation of nonenzymic histone damage with aging [36].…”

Fate of newly synthesized histones in G1 and G0 cells

“…However, there is some evidence for histone exchange. The half-life of liver histones in mice was 117 days as compared to 318 days for DNA, thus indicating some turnover of histones [14]. If nucleosomes do slowly turn over, the histone composition of the core particles should ultimately reflect any changes in the synthesis pattern of histone variants.…”