Histone Modifications Sample Clauses

Histone Modifications. In cells, DNA is tightly packed and organized around proteins known as histones, in approximately 146bp units known as nucleosomes. In mammals, histones are found in octamers with two copies each of X0X, X0X, X0, and H4, each of which is subject to post- translational modifications including methylation, acetylation, phosphorylation and numerous other modifications at various residues. Since the 1960s it has been clear that such modifications influence gene expression31. These modifications can broadly be divided into activating and respressive marks, although many marks play more complicated roles, that collectively compose the 'histone code', a set of instructions to cells dictating gene expression. Intrinsic to the histone code are 'writers', 'readers', and 'erasers', which enzymatically modify histones to respectively add, recognize, or remove these modifications. Each unique xxxx has its own family of regulators. For example, most histone lysine methylases (writers) contain a SET domain, named for the founding members of the family in Drosphila (Su(var)3-9, Enhancer of zeste, and trithorax). And while DOT1L, the writer of H3K79me, possesses a distinct enzymatic domain, both families use S-adenosylmethionine (XXX) as a cofactor/methyl-donor. There are also two families of lysine demethylases (erasers), amine oxidases (like LSD1) and iron-dependent dioxigenases, which contain a jumonji-C domain (such as JMJD1C). Reading of lysine methylation can be accomplished by a slew of methyl-lysine-binding domains including PWWP domains, WD40 repeats, PHD fingers, ankyrin repeats, and members of the Royal superfamily: chromodomains, chromobarrels, Tudor domains, and MBT repeats, among others. Among the most important modifications associated with active transcription is methylation of H3K4. Nearly a dozen distinct histone methylases and demethylases can act on H3K4 in different cell types and contexts, and perhaps dozens of readers recognize the different methylation states (me0-me3)32. Xxxxxxxxxxx X0X0xx states are associated with greater levels of transcriptional initiation. H3K4me1 tends to be associated with enhancer elements (discussed below), which display modest transcription of enhancer RNAs (xXXX). H3K4me3 tends to be found at active promoters, especially promoter CGI. H3K4me2 is less studied, but is typically linked to the transition between H3K4me1 and H3K4me3. Methylation of H3K4 is tightly linked to histone acetylation, which can occur at many lysine ...

Histone Modifications. Histones are alkaline proteins which package DNA molecules into structural units known as nucleosomes. The nucleosome core consists of a 146 bp DNA string, wrapped in 1.67 left-handed superhelical turns around a histone octamer. The octamer includes two H2A, two H2B, two H3, and two H4 histones, which are held in place by one H1 molecule, binding a 20-80 bp linker region (Luger, Xxxxx et al. 1997). The N-terminal tails of histones can undergo a number of post-translational modifications (e.g. methylation, acetylation, phosphorylation, ubiquitination, SUMOylation, and citrullination, see Table 1.3.1.2.1), which affect their interactions with DNA molecules. Some of these modifications have been the object of in depth studies, which have demonstrated their association with transcriptionally active genomic regions. For instance, tri-methylation of histone H3 lysine 4 (H3K4me3) and acetylation of histone H3 lysine 9 and 14 (H3K9ac and H3K14ac) are marks of actively transcribed promoters. Conversely, H3K36me3 is a modification that is typically found in the body of actively transcribed genes, whereas H3K9me3 proteins co-localise with constitutively repressed genes (Table 1.3.1.2.2) (Xxxxxx, Cuddapah et al. 2007; Kouzarides 2007). Of note, novel histone modifications are still being discovered and recent mass- spectrometry experiments have greatly expanded the catalog of known marks (Xxx, Luo et al. 2011). 42 42