Histone variants

Histones are small, basic proteins required to condense DNA into chromatin. They have been first described and named in 1884 by Albrecht Kossel. There are five main histones HI, H2A, H2B, H3 andH4. An octamer of core histones H2A, H2B, H3 andH4 is located inside a nucleosome, the central building block of chromatin, with about 150 base pairs of DNA wrapped around. The basic nature of histones, mediated by the high content of lysine and arginine residues, allows a direct interaction with the acidic phosphate back bone of DNA. The fifth histone HI is located outside at the junction between nucleosomes and is referred to as the linker histone. Besides the main histones, so-called histone variants are known, which replace core histones in certain locations like centromers. 

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 use of urea triton gel electrophoresis (Zweidler and Cohen, 1972 Alfageme et al., 1974) has permitted the further resolution of histone fractions and the identification of histone variants. Microcomponents or variants of histone HI have been known for a long time (for references, see Cole, 1977). Recently, it has been shown that microcomponents or variants of histones H2B, H2A, and H3 occur in many systems (Marzluff et al., 1972 Laine et al., 1976 Garrard, 1976 Blankstein and Levy, 1976 Zweidler, 1976 Franklin and Zweidler, 1977). Furthermore, in sea urchin embryo the synthesis of new histone variants has been correlated with development (Cohen et al., 1975 Newrock et al., 1978 Von Holt et al., 1979). 

Abstract Histone variant are non-allelic forms of the conventional histones. They are expressed... 

The histone variants of H2A form the largest family of identified histone variants (Redon et al, 2002 Sarma and Reinberg, 2005). This could be associated with both the strategic position that has the histone H2A within the histone octamer and the less stable interaction of the H2A-H2B dimmer with both DNA and the (H3-H4)2 tetramer within the nucleosome (Luger et al, 1997). Most of the histone H2A variants exhibit a unique property in addition to the N-terminal tail domain, they also posses an unstructured C-terminal tail. To date four variants of histone H2A have been discovered. These include, H2AZ, H2A.X, macroH2A and H2A.Bbd. The highest differences in the primary structure of these H2A variants are observed in their C-terminal portion. Each of these variants could be efficiently incorporated in the nucleosome in vitro and in vivo. The presence of these variants alter the structural and functional properties of the nucleosome distinctly. 

HISTONE VARIANTS AND DISEASE 6.1. Histone Variants and Cancer... 

Angelov D, Molla A, Perche PY, Hans F, Cote J, Khochbin S, Bouvet P, Dimitrov S (2003) The histone variant macroH2A interferes with transcription factor binding and SWI/SNF nucleosome remodeling. Mol Cell 11 1033-1041... 

Angelov D, Verdel A, An W, Bondarenko V, Hans F, Doyen CM, Studitsky VM, Hamiche A, Roeder RG, Bouvet P, Dimitrov S (2004) SWI/SNF remodeling and p300-dependent transcription of histone variant H2ABbd nucleosomal arrays. Embo J 23 3815-3824... 

Bao Y, Konesky K, Park YJ, Rosu S, Dyer PN, Rangasamy D, Tremethick DJ, Laybourn PJ, Luger K (2004) Nucleosomes containing the histone variant H2A.Bbd organize only 118 base pairs of DNA. Embo J 23 3314-3324... 

Dhillon N, Kamakaka RT (2000) A histone variant, Htzlp, and a Sirlp-like protein, Esc2p, mediate silencing at HMR. Mol Cell 6 769-780... 

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