Histone modification mechanisms

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... 

Sadri-VakiU G, Cha JH (2006) Mechanisms of Disease Histone modifications in Huntington s disease. Nature Qinical Practice Neurology 2(6) 330—338... 

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. 

Knowledge of the detailed mechanism underlying circadian rhythms continues to be refined as new experiments reveal novel facets of the oscillatory machinery. Thus, a link has recently been established between chromatin structure and the circadian oscillatory mechanism. The CLOCK protein indeed functions as a histone acetyltransferase [116]. This enzyme activity is required for oscillations so that histone modification and the associated chromatin remodeling are implicated in the origin of circadian rhythmicity. 

One possible function for H3.3 and some of the other replacement variants is to maintain the integrity of chromatin structure by replacing histones that are damaged or lost during normal cellular metabolism. Ahmad and Henikoff [104] suggested that replication independent incorporation of H3.3 could provide a mechanism to switch patterns of histone modification by removing H3 molecules that may be irreversibly modified by methylation. They also suggested that H3.3 could serve as a mark of transcriptionally active chromatin. One complication for... 

Epigenetics refers to the inheritance of information from a single cell to another, independent of the DNA sequence. Epigenetic mechanisms include DNA methylation, histone modifications, and, more recently, a variety of noncoding RNAs (ncRNAs). These mechanisms have been extensively reviewed elsewhere (7). Here, we briefly summarize them and emphasize those features relevant in the field of epigenomics. 

The phosphorylation of histone H3 can have a repressive or activating effect on transcription. Members of the MAP kinases (see Chapter 10) that are responsible for this phosphorylation have been identified, providing a link between growth factor stimulation and transcription activation at the level of histone modification. H3 phosphorylation has been also recognized as part of a complex signaling mechanism that operates in the condensation/decondensation of chromatin during the cell cycle. Furthermore, histone HI phosphorylation has been linked to the relief of transcription repression. 

Mechanisms by Which Histone Modifications Achieve Transcriptional Regulation... 

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