Chromatin proliferating cells

Milutinovic S, Zhuang Q, Szyf M. Proliferating cell nuclear antigen associates with histone deacetylase activity, integrating DNA replication and chromatin modification. J Biol Chem 2002 277 20974-20978. 

Close observations of immunofluorescence signals showed that there are three different staining patterns, which correspond to three different nucleolar compartments FC (Fibrillar center), DFC (dense fibrillar component), and GC (granular component). Nucleolus is surrounded by heterochromatin. When the cells are in very active state of its proliferation, the nucleolar compartments and heterochromatin are integrated into a highly intricate structure called nucleolonema . A recent study has suggested that the chromatin associated with the nucleolus is less mobile than... 

These examples demonstrate that nucleolin could be a therapeutic target for the development of innovative molecules against cancer and virus infection. The newly described function of nucleolin in chromatin dynamics and gene expression is potentially another function of nucleolin that could be targeted for the search of specific inhibitors of cell proliferation. 

Studies with native and reconstituted chromatin show that phosphorylated HI destabilize chromatin structure [62,63]. Phosphorylation of HI increases the protein s mobility in the nucleus and weakens its interaction with chromatin [64,65]. In studies with avian fibroblasts transfected with H5 (an HI variant), H5 was shown to inhibit proliferation in normal fibroblasts but not in transformed cells, in which H5 was phosphorylated. Aubert et al. proposed that phosphorylated H5 lacked the ability to condense chromatin [66]. The greater affinity of the dephosphorylated relative to phosphorylated HI for chromatin may interfere with the performance of chromatin remodeling agents. For example, dephosphorylated, but not phosphorylated, HI inhibited chromatin remodeling by SWI/SNF [67]. Thus, these and other studies provide support for the idea that an increase in the phosphorylation of HI leads to destabilization of the chromatin [24]. 

On the other hand, there is strong evidence that the effects of flavonoids on cultured cells are not merely toxic but via induction of apoptosis or inhibition of proliferation. Thus signs of apoptosis, such as induction of caspase-3, fragmentation of DNA and chromatin condensation, are frequently detected upon cell exposure to flavonoids [213, 217-221]. In addition, the effects of flavonoids are generally reversible upon removal or addition of serum [222-224]. 

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