Chromatin terminally-differentiated cells

Phosphorylation of specialized linker histones (such as histone H5 or sperm-specific HI histones) has also been shown to have a major role in the chromatin folding processes leading to the highly condensed chromatin structure which is present in the nuclei of terminally differentiated cells such as bird erythrocytes [172] and histone-containing sperm nuclei [115,118]. In this later instance. 

The methylation of DNA at CpG islands has also turned out to be an important regulator for cell development, the differentiated proteome and the regulation of cell survival [237,238]. Indeed the implications of this chemical modification have been linked to DNA accessibility, chromatin fluidity and cell transformation [239,240]. DNA methylation is required for genomic stability and believed to act as an inert epigenetic marker in germinal cells and preimplantation embryos [238]. Presumably, DNA methylation is required for the heritable transmission of chromatin structure, which prevents the expression of terminally silenced genes in differentiated tissues, and provides a host-defense mechanism against parasitic transposable elements [241]. 

The finding that nearly all of the conjugates except modified histone H2B and poly-(ADPR) synthase itself are also present in untreated normal hepatocytes (Figs. 5 and 6), supports the view that these proteins may be involved in other chromatin functions in addition to DNA repair. It is tempting to speculate that the higher degree of ADP-ribosylation of most of these proteins in the normal hepatocyte (Fig. 6 nh and It) as compared to the hepatoma cell (Fig. 6 hp) may be related to the terminally differentiated state of the normal liver cell. 

Accordingly, some effort has been devoted to studying the effects of cisplatin on transcription. In vitro experiments with RNA polymerases demonstrated that productive elongation activity was prematurely terminated by the whole spectrum of cisplatin-DNA adducts, but not by the /ran.y-DDP 1,3-intrastrand adducts [150-152], Selective bypass of trans-DDP adducts was also demonstrated in XPA cells, suggesting that repair of the DNA lesions did not contribute to differential transcription inhibition by the platinum compounds [153], In vivo, hormone-induced chromatin remodeling and subsequent transcription from the MMTV promoter was specifically inhibited by cisplatin [154], In this case, platinum adducts seemed to cause a decrease in the DNA binding of one of the transcription factors, NF1. Several chromatin-associated proteins, such as the linker histone protein HI or... 

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