Briefings in Functional Genomics and Proteomics Advance Access originally published online on September 2, 2006
Briefings in Functional Genomics and Proteomics 2006 5(3):177-178; doi:10.1093/bfgp/ell031
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Editorial
How does one package several meters of rope into a poppy seed? Eukaryotic cells face a similar problem when packaging their genomic DNA, which can be several meters long, into the small dimensions of the nucleus. Cells have solved this problem by compacting genomic DNA through the association of DNA with proteins, mainly histones, into a refined DNA-protein complex termed chromatin. Histones are the basic packaging material for DNA and the building blocks of the nucleosome, the smallest structural unit within chromatin. The nucleosome consists of 146 bp of DNA wrapped around a core-histone octamer, consisting of two copies each of the four core-histones (H2A, H2B, H3 and H4), and can contain a linker-histone H1. Nucleosome assembly allows for the compaction of genomic DNA into higher-order chromatin structures. Although the precise mechanisms of chromatin compaction remain to be uncovered, interactions among and between nucleosomes and non-histone proteins are believed to contribute to the formation of compacted, higher-order chromatin structures. In addition to being essential for the packaging of DNA, a plethora of old and new studies indicate that histones play an important role in the control of DNA-templated processes. Histones are the target of various post-translational modifications such as acetylation, methylation, phosphorylation and ubiquitination. Although histone modifications were discovered in the early 1960s, and studies in the early 1970s had correlated histone acetylation with transcription in chromatin, the first enzyme, which directly modifies a histone (in this case histone acetylation), was discovered almost 30 years later in 1996. Ignited by this initial discovery, a global research effort resulted in the identification of a large number of enzymes that e.g. acetylate, methylate and ubiquitinate histones, and has provided intriguing insights into the role and function of histones and their modifications in the execution of DNA-dependent processes. Current data support models in which specific histone modification patterns dictate the function of the packaged DNA. For example, the acetylation of histones H3 and H4 has been correlated with transcriptional activation, while methylation of single lysine residues in H3 (lysine 9 or lysine 3) mediates silencing. Most interestingly, proteins have been identified that recognize and bind modified histones and convert histone modifications into a biological response. Based on the accumulated data, it appears possible that histone-modification patterns represent a novel code that determines the function of DNA in the nucleus of eukaryotic cells. Cells can contain several variants of each histone and the function of those variants is only now being investigated. Recent studies have correlated specific histone variants with distinct biological processes such as mitosis and transcription and have added yet another level of complexity to histone function in the nucleus. However, many questions addressing, for example, the global interplay of the various histone modifications and the function of the many histone variants, remain to be answered in the exciting field of research.
In this issue of Briefings in Functional Genomics and Proteomics, we have assembled a number of articles by experts in the field, which provide in-depth descriptions and future outlooks in various area of histone research.
Polyubiquitination of proteins is a death signal, as it triggers protein degradation by the proteasome. Ubiquitin was originally discovered as a peptide covalently bound to histones, long before its role in protein degradation was discovered. All histones can become mono-ubiquitinated in cells and, interestingly, mono-ubiquitinated histones stay associated with chromatin rather than being degraded. This issue begins with a review by Mary Ann Osley (University of New Mexico School of Medicine, Albuquerque, USA) describing recent advancements in the role of histone ubiquitination in the execution of DNA-dependent processes.
Acetylation is the best-characterized histone modification playing important roles in chromatin assembly and control of DNA-templated events. Contributions by M. Horikoshi (University of Tokyo, Tokyo, Japan) and E. Mauro (Universita La Sapienza, Rome, Italy) describe the role of histone acetylation and deacetylation in DNA-dependent processes.
The establishment and maintenance of mitotically- and meiotically-stable (epigenetic) gene expression patterns is fundamental for cell differentiation. Histone modifications are believed to play an essential role in epigenetic gene expression, as epigenetic regulators can modify histones. The paper by A. Imhof (Ludwig-Maximillians University of Munich, Munich, Germany) reviews and discusses the intricate connection of epigenetics and histone modifications.
The exciting field of histone variants is described in a contribution by J. Ausio (University of Victoria, Victoria, Canada), summarizing and discussings the biological function of histone variants.
The contributions will provide the interested reader with up-to date information on this fast moving research area, represent useful references for the interested researcher, and we hope will promote and stimulate future research efforts that will address the many unsolved problems in the field.
The realization of this issue of Briefings in Functional Genomics and Proteomics would not have possible without an untiring effort by the staff from Oxford Journals whom I would like to thank at this point.
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