Histone fold domains

Figure 1. Variants of the histones H3 from yeast Saccharomyces cerevisiae S.c.), fruit fly Drosophila melanogaster D.m), and human Homo sapiens H.s.). H3.1 is identical to H3.2 with the exception of a serine to cysteine exchange (top). H3.3 differs from H3.1/H3.2 only in four amino acid positions. Centromer-specific histones (CenH3 s) have an amino terminus of variable length (between 20 and 200 residues). They also possess an extended loop 1 region in the histone fold domain...

Although the histone fold was first described from the structure of the histone octamer core of the nucleosome [17], the high a-helical content was predicted much earlier [43]. The core histones possess three functional domains (1) the histone fold domain, (2) an N-terminal tail domain, and (3) various accessory helices and less structured regions. The N-terminal tail domains of the core histones are currently the focus of intense research. Covalent modifications of residues in these unstructured domains appear to modify local chromatin structure, either directly or... 

Despite many biochemical similarities between linker and core histones the proteins of these two groups differ in architecture, evolutionary origin, and function. Each of the four core histones has a characteristic histone fold domain. The latter is an old and ubiquitous structural motif used in DNA compaction and protein dimerization [3]. Linker histones do not have a histone fold. The canonical... 

Sullivan, K.F., Hechenberger, M., and Masri, K. (1994) Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere. J. Cell Biol. 127, 581-592. Choo, K.H. (2000) Centromerization. Trends Cell Biol. 10, 182-188. 

Chen, Y., Baker, R.E., Keith, K.C., Harris, K., Stoler, S., and Fitzgerald-Hayes, M. (2000) The N terminus of the centromere H3-like protein Cse4p performs an essential function distinct from that of the histone fold domain. Mol. Cell. Biol. 20, 7037-7048. 

From a structural perspective, histones can be considered to consist of a tri-partite organization in which a central histone fold domain [81] is flanked by N- and C-terminal regions tails with a low level of folding. The histone fold is responsible for the histone bundle and handshake interactions that hold the histone octamer together [45,265,307,308] while the tails do not appear to have any major role in the stability of the octamer subunits [309]. 

The discovery of the histone fold domain in TAFs began with Drosophila TAF9 and TAF6, which have significant sequence similarity with the histone fold domains of histone H3 and H4, respectively. A cocrystal structure of the histone fold domains of these two TAFs shows that they interact and form a heterotetramer, similar to that of histone H3 and H4... 

The ability of the histone-like TAFs to form an octamer-like structure raises the possibility that the TAF octamer may wrap promoter DNA in a manner similar to the nucleosome (Hoffmann et al., 1997 Oelgeschlager et al., 1996). This hypothesis is supported by the resemblance of DNase I footprinting patterns of TFIID on the Adenovirus Major Late (AdML) promoter to those of nucleosomal DNA. However, the arginine side chains in histones that form primary contacts with DNA are not conserved in TAFs (Luger et al., 1997). Therefore, the histone fold domain interaction may be used only for the formation of a compact structure and is not necessarily involved in DNA wrapping. 

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