Nuclear Structure Modifications in the Control of Gene Expression and Cell Function
In a recent review1 we have presented evidence for the organization of DNA from its lowest (bp sequence) to its highest structure, as emerging from a wide variety of biophysical and biochemical measurements conducted on cells of diversified functional states. The changes occurring at the level of the nuclear structure were determinant in building a firm basis for the high order chromatin structure, from the nucleus to the genes, namely the “fibrosome” model which identified within the 300 Å chromosome-sized fiber a fundamental repeating unit about 17 Kbp long, arranged drapery-like near the nuclear envelope or the nucleoli and capable of undergoing transitions between three discrete states of DNA superpackingl1. Without such a working model to be constantly challenged and updated, any exploration of the numerous modifications occurring during cell proliferation and transformation could be nothing more than a fishing expedition. Some of the changes induced are indeed horrifying in their complexity (cycles within cycles) and heterogeneity (membrane versus cytoskeleton, cytoplasmic proteins versus nuclear chromatin, acetylation versus phosphorylation of histones, HMG versus H1). An excellent account of most recent findings is given in multi-authored books2–4. Despite the jungle of “descriptive” cellular events (with recurrent logic where viral oncogenes are now substituting for serum stimulation) and the “zoo” of specific molecules (such as cyclic nucleotides, HMG, “growth factors”, H1, viral proteins, microtubules, glycoproteins), critical steps can be identified, and where feasible, will be summarized here within a coherent framework for gene expression compatible with the above model for chromatin and gene structure.
KeywordsHydration Cage Titration Adduct Macromolecule
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