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We studied the relationship between polymorphisms rs1800629 (-308G>A), rs28362491 (-94ins>del), and rs3834129 (-652ins>del) in the promoter regions of TNFA, NFKB1, and CASP8 genes, respectively, encoding TNF-α, nuclear transcription factor κB1 (NF-κB1), and caspase 8 (CASP8), and the risk and stages of chronic lymphocytic leukemia in ethnic Russians, residents of the Vyatka region of Russia. Allele -308A, genotype -308AA, and -308A genotypes (-308AA/-308AG) were associated with the risk of this pathology (OR=1.64, 95%CI 1.14-2.37, p=0.007; OR=4.48, 95%CI 1.20-16.80, p=0.02, and OR=1.57, 95%CI 1.05-2.36, p=0.03). In addition, NFKB1 allele -94del and genotype -94del/del were associated with advanced stages of the disease at the time of diagnosis (OR=0.66, 95%CI 0.46-0.97, p=0.03 and OR=0.43, 95%CI 0.20-0.92, p=0.03). These data suggest that -308G>A and -94ins>del polymorphisms of genes TNFA and NFKB1, respectively, can be involved in the pathogenesis of chronic lymphocytic leukemia.

Localization of immunogenic tissue-specific proteins in chromatin regions, hypersensitive to endogenous nucleases, has been studied using rabbit antibodies against rat thymus chromatin. It is shown that the first 1–2,5% of the chromatin (calculating on DNA), released by Mg2+-, Mn2+-, and Ca2+/Mg2+-dependent nuclear endonucleases are drastically enriched in tissue-specific antigenic determinants. The released chromatin fractions are found to contain a heterogeneous set of nonhistone proteins and are deficient in histones. The cleavage of nuclear DNA by endogenous acidic nuclease, independent on bivalent ions, resulted in a significantly less enrichment of the released fractions with immunogenic proteins.

The properties of rat liver and thymus non-histone and nuclear sap proteins were compared. The distribution of total, labile-bound and 0.35 M NaCl extractable non-histone proteins from one organ on polyacrylamide-gel electrophoresis in the presence of sodium dodecylsulphate is quite similar. On electrophoresis non-labelled and 32P-labelled non-histone and nuclear sap proteins from one organ differ from one another both qualitatively and quantitatively. We did not find an appreciable difference between non-labelled non-histone proteins isolated from liver and thymus. The distribution of 32P-labelled non-histone proteins from various organs differs quantitatively rather than qualitatively. Non-labelled and 32P-labelled nuclear sap proteins from liver and thymus differ significantly. 'Free' nuclear sap proteins and the proteins of ribonucleoprotein particles from thymus nuclei contain a great quantity of identical polypeptides, whereas other polypeptides are specific to each of these protein fractions. Upon incubation of nuclei with [gamma-32P]ATP the label is incorporated into all the fractions of nuclear protein. The nuclear proteins are phosphorylated at decreasing rates in the order: labile-bound non-histone proteins greater than firmly bound non-histone proteins greater than 'free' nuclear sap proteins = proteins of ribonucleoprotein particles greater than histones. Nuclear sap and non-histone proteins contain protein kinases capable of phosphorylating both these proteins and histones. Histone phosphorylation is sharply inhibited after addition of DNA, the protein kinases of nuclear sap phosphorylating less effectively the histones complexed with DNA than the non-histone proteins. Both non-histone and nuclear sap proteins contain fractions interacting in vitro with DNA. Denatured DNA binds twice as much 32P-labelled nuclear sap proteins and a little more 32P-labelled non-histone proteins than native DNA. Denatured DNA binds non-histone and nuclear sap proteins much more effectively than native DNA. It was shown by the membrane filter technique that the major part of the nuclear sap and non-histone proteins interacting with native DNA binds to it non-specifically. A certain portion of non-histone and nuclear sap proteins interacts specifically with homologous denatured DNA. The possible role of non-histone and nuclear sap proteins in the regulation of transcription is discussed.