Histone modification system

It has also been realized that histone modification patterns and levels are an important aspect when studying diseased gene expression states. For instance, it has recently been shown that certain aberrant posttranslational histone modifications are associated with the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) [381]. In this study, MS combined with stable isotope labeling was used to differentially analyze histone modifications in splenocytes from a mouse model of SLE. Compared to the control, the disease model showed a global site-specific hypermethylation, except for H3K4, and hypoacetylation in histone H3 and H4. 

The similarity of the various histone fibers is probably correlated with the similarity in the distribution of the amino acids in the sequences of the four core histones and reflects their function as the skeleton or backbone of chromatin. However, from the presence of a specific pattern of interactions of the core histones and the existence of histone variants and histone postsynthetic modifications, one can anticipate modulations in the basic general pattern of histone structure. In Section V, a possible mechanism for histone microheterogeneity influencing chromatin structure is suggested. Analogous to other assembly systems, small subunit modifications may be amplified to produce major changes in the assembled superstructure. 

The present study represents an attempt to characterize the proteins undergoing poly-(ADP-ribose) modification in association with myogenesis. Although we have not yet performed analysis of poly(ADP-ribose) conjugates of histones which are the main acceptors in many systems [20, 21], several interesting observations have emerged from our study. 

These modifications were also associated with a high level of poly(ADP-ribosyl)ation of the enzyme. Furthermore we have found that upon poly(ADP-ribose) glycohydrolase action on poly(ADP-ribosyl)ated chromatin, modification of histone H2B was more resistant than modification of other nucleosomal proteins (8). Menard et aL (9) have also shown, in a reconstituted in vitro poly(ADP-ribose) turnover system, that the half life on various acceptor proteins is quite different. These results suggest that the preferential distribution of poly(ADP-ribose) on nuclear proteins is related on the one hand to the localization of the enzyme on active (Hl-depleted) and inactive (native) chromatin and on the other hand to the turnover rate of poly(ADP-ribose) on the enzyme which then determines the pattern of poly(ADP-ribosyl)ation of nuclear proteins. We will discuss in the last section the preferential distribution of die enzyme in the nucleus. 

Repression by Histones in vivo. The experiments in a cell-free system still leave several questions unanswered. Therefore attempts were made to approach the question of repression by the histones from a different angle. Thus, Fellenberg and Bopp succeeded in impairing a few morphogenetic processes which require certain genetic activities by treatment with histones. The formation of new roots in isolated pea epicotyls which is induced by lAA, the formation of wound phelloderm in Kalanchoe daigremontianum, and the formation of crown galls, were all inhibited by administration of histones from various sources. Certain chemical modifications of the histones (by acetylation, oxidation. 

---