Histones biological functions

The purpose of this article is to correlate the rather unique structural aspects of the five histone molecules—the differences among them as well as their similarities—with their biological function. Such an analysis is best approached, we believe, via a study of the many protein-protein (Section II) and protein-DNA (Section III) interactions in which the histones participate. Emphasis will be placed on the four core histones H2A, H2B, H3, and H4 HI will be discussed briefly, mainly in relation to its interaction with DNA. In no sense is the bibliography meant to be exhaustive. 

Similar results were obtained from reconstitution experiments with DNA and a non-cross-linked octamer (Thomas and Butler, 1978). Nucleosome-like particles were observed in the EM and a pattern of histone cross-linking comparable to that of native chromatin was obtained. However, only 140-base-pair repeats were obtained upon micrococcal nuclease digestion instead of 200-base-pair repeats obtained for native rat liver chromatin (Noll and Komberg, 1977). This indicates that, in the absence of HI, only core particles can be reconstituted. Nevertheless, these studies with both cross-linked and reassembled un-cross-linked histones demonstrate that the octamer is a complete biological functional unit retaining the information for folding the DNA around the histone core. 

These studies demonstrate that H2A (T119) phosphorylation by NHK-1 regulates mitotic and meiotic progression. However, it remains unclear what is the biological function of other histone H2A posphorylation sites and how they impact the many other histone modifications. 

The biological function of ADP-ribosylated nuclear proteins is not clear. Poly-(ADP-ribose) synthetase has been reported to be stimulated by histones, but histones themselves do not serve as acceptors in vitro (42). The endogenous acceptor iji vivo might involve proteins other than histones. Recently an enzyme that cleaves the ADP-ribosyl histone linkage has been purified from rat liver (43). 

Most of the components that conuihute to cellular homeostasis are proteins—so much so that more than half of the dry weight of a cell is protein. Histones, cellular enzymes, membrane transport systems, and immunoglobulins are just a few examples of the proteins that carry out the biological functions of a living human cell. Proteins are hydrated three-dimensional structures, but at their most basic level, they are composed of linear sequences of amino acids that fold to create the spatial characteristics of the protein. These linear... 

DNA Is Involved In several biological functions requiring substantial changes In conformation. For example, the Intrinsically stiff DNA molecule Is wrapped fairly tightly about histones In nucleosomes, and this entire complex must be partially unraveled during replication and transcription. The ability of DNA to assume several different conformational forms In response to Its solid and solution environments has been evident for some time. Recent applications of spectroscopic methods sensitive to molecular dynamics have Indicated that double stranded DNA can also undergo rapid local motions of significant amplitude. 

Histones occur in the chromosomes of organisms with genuine cell nuclei, for example, in the chromosomes of the thymus gland. The biological function of histones is largely unknown. They probably regulate replication or transcription. Histones are complexed with nucleic acids (nucleohistones) in organisms. 

Poly ADP-ribose groui are found in eukaryotic chromosomal proteins, mitochondrial proteins and histones. The biological function of the ADP-ribosylation of proteins in eukaryotic cells is not known. 

Hnilica, L. S. The structure and biological function of histones. Cleveland Chemical Rubber Co. 1971. 

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