Histone modification expression

In the nuclei of all eukaryotic cells, DNA is tightly wrapped around an octamer of histone proteins and is compacted into a dense structure known as chromatin. In order to access the genetic information which is required in numerous essential cellular processes including DNA replication, gene expression and DNA repair, chromatin needs to be partially unwound. One important mechanism to regulate chromatin structure and thus to control the access of the genomic DNA is through histone modifications [1-6]. The histone octamer is composed of two copies of H2A, H2B, H3 and H4 core histone proteins. Their tails, that protrude out of the surface of the... 

Ueda K, Kinoshita Y, Xu ZJ, Ide N, Ono M, Akahori Y, Tanaka I, Inoue M (2000) Unusual core histones specifically expressed in male gametic cells of Lilium longiflorum. Chromosoma 108 491—500 Unal E, Arbel-Eden A, Sattler U, Shroff R, Lichten M, Haber JE, Koshland D (2004) DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain. Mol Cell 16 991-1002... 

Recent studies have demonstrated that histone H4 (SI) phosphorylation is also a key role in the response to DNA double-strand breaks, cell-cycle progression and gene expression. In particular, this modification may have important roles during mitosis and S-phase-associated events in the cell-cycle and its phosphorylation found on newly synthesized histones during S-phase. However this phosphorylated residue is a novel histone modification site, and the details of this mechanism will be made evident by future experimentation. 

DNA methylation may directly decrease the binding affinity of certain transcription factors to DNA [38]. Additionally, methylated CpG sites recruit MBD proteins, which in turn leads to transcriptional repression [39]. siRNA-mediated knockdown of MBD proteins leads to a re-expression of silenced tumor suppressor protein candidates [40]. DNA methylation and histone modification are dependent on each other [41, 42] and from this interplay a synergy in derepression (e.g. between histone deacetylase and DNMT inhibitors) can be observed [43—45] (see also below). 

Fahrner, J.A., Eguchi, S., Herman, J.G. and Baylin, S.B. (2002) Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Research, 62, 7213-7218. 

The previous uncertainty gave rise to the signaling pathway model. It acts as a more general model to explain the role of so many histone modifications on gene expression (18). It states that histone modifications can serve as... 

Summary of effect of different histone modifications v on gene expression. ... 

Although ncRNAS are not strictly part of the epigenetic machinery, there is evidence that some of them may actually work as epigenetic regulators since they can interfere with the epigenetic machinery (DNA methylation and histone modifications), thus influencing gene expression (see Section 2.2) (26,27). 

Histone modifications, such as phosphorylation, acetylation, and methylation, regulate gene expression. " Histone lysine methylation was considered a static modification, until relatively recently, when histone demethylases were discovered." One such enzyme is ESDI, which belongs to the amine oxidase superfamily. ESDI catalyzes the demethylation of mono- and disubstituted Eys 4 of histone H3" in a reductive halfreaction very similar to those catalyzed by DAAO and MAO by oxidizing the amino group of the methylated lysine to the corresponding imino product, which hydrolyzes nonenzymatically to formaldehyde (Equation (2)). 

In this book, I will use the term gene expression to refer to the ultimate production of a protein or RNA molecule derived from the information stored in DNA. Gene expression can be blocked, changed, or regulated, and its changes apparently can occur in three main ways (i) in the DNA molecule itself (for example, DNA methylation) (z) in the way DNA is folded and arranged to form the chromosomes (for example, histone modification) and (3) biochemically anywhere between the read-out of DNA and the synthesis of the ultimate product determined by that piece of DNA code (for example, RNA interference). 

In general, transcriptional activators can bind and recruit HATs while transcriptional repressors and corepressors interact with HDACs. The unwinding of DNA offhistones by lysine acetylation is conceptually helpful for understanding the action of HATs and HDACs. It is, nevertheless, a simplistic and incomplete explanation for the way in which these enzymes control gene expression. For example, in some cases [4] inhibition of HDACs can lead to a counterintuitive decrease in gene expression. It is likely that the overall pattern of histone modification (of which acetylation is but one example) represents... 

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