Regulation of Gene Expression by Poly(ADP-ribosyl)ation

多(ADP-核糖)合成与染色质有关，一些核蛋白是由该酶聚合的(ADP-核糖基)。然而，这种修饰的生理作用仍不清楚。为了检测多聚ADP-核糖化对基因表达的影响，我们首先建立了一种通过抗酶抗体来测量组织和细胞中该酶的含量的方法。我们测定了神经生长因子诱导大鼠嗜铬细胞神经分化过程中酶的含量变化。在此过程中，酶的水平有所下降。妊娠早期兔子宫上皮细胞合成子宫球蛋白是由孕酮诱导的。我们试图确定……的数量变化。子宫红蛋白诱导过程中的酶。然而，该酶的水平不够大，不能用抗体方法测定。因此，我们克隆了该酶的编码基因。我们以该基因为探针，研究了该酶在小鼠巨噬细胞肿瘤细胞系分化过程中的表达水平。在干扰素存在下培养2天后，该酶的mRNA含量下降到未处理细胞的20%，而Ia抗原。其中一个组织可分解性基因产物被显著诱导。我们得出结论，这种酶在某种程度上参与了基因调控。尤其是在分化过程中。

Poly(ADP-ribose) syntheate is associated with a chromatin and some nuclear proteins are poly(ADP-ribosyl)ated by the enzyme. However, the physiological role of the modification is still unclear. In order to examine tne effect of poly(ADP-ribosyl)ation on gene expression we first established a method to measure the amount of the enzyme in tissues and cells by the antibody against the enzyme. We determined the change in the amount of the enzyme during the neural differenciation of rat chromafin cells induced by nerve growth factor. The level of the enzyme was decreased during the process. Synthesis of uteroglobin in rabbit uterine epithelial cells during early pregnancy is induced by progesterone. We attempted to determine the change in the amount of. the enzyme during the uteroglobin induction process. However, the level of the enzyme was not large enough to determine by the antibody method. Thus, we isolated a cDNA clone coding for the enzyme. We use the cDNA as a probe to estimate the level of mRNA for the enzyme during the differenciation of murine macrophage tumor cell line. The amount of mRNA for the enzyme decreased to 20% of that for the untreated cells by 2 days after incubation in the presence of <gamma> -interferon, while the Ia antigen. one of the histocompartibility gene products, was markedly induced. We conclude that the enzyme in somehow involved in the gene regulation. especially during differnciation.