Histones Drosophila

Efforts to identify specific inhibitors of histone methyltransferases are in their early stages, and only two specific KMT inhibitors have been identified. The fungal mycotoxin chaetocin (9, Figure 2) inhibits the KMT Su(var)3-9 from Drosophila with an IC50 of 0.8 iM and produces a... 

Figure 3. The stability of the nucleosome is affected by the length and the superhelicity of DNA. (a-b) The chromatin fibers were reconstituted from the purified plasmids and the histone octamers by a salt-dialysis method and observed under AFM. The 3 kb (a) or 106 kb (e) supercoiled circular plasmid was used as a template, (c) Relationship between the plasmid length and the frequency of nucleosome formation in the reconstitution process. The nucleosome frequency is represented as the number of base pairs per nucleosome and plotted against the length of the template DNA in supercoiled (filled circle) and linear (open circle) forms, (d) AFM image of the chromatin fiber reconstituted on the topoisomerase 1-treated plasmid, (e) Chromatin fiber reconstituted with Drosophila embryo extract. The chromatin fiber was reconstituted from plasmid DNA of 10kband the embryo extract of Drosophila, and was observed by AFM...

Acetylation of the histone tails correlates with the activities of genes (Kimura et al., 2005). However, the detailed analyses of the acetylation on the individual lysine residue have revealed that the relationship between the acetylation and the chromatin-compaction is not simple. There are 1-6 lysine residues in each histone subunit, that could be acetylated the Lys of H2A, Lys, Lys, Lys, and Lys ° ofH2B, Lys , Lys , Lys, Lys, Lys, andLys of H3, and Lys, Lys, Lys, and Lys of H4. In mammal, more than ten HATs (7/istone Acetyl Transferases) have been identified, each of which acetylates a specific lysine residue. Acetylation frequently occurs in euchromatin regions, and some in heterochromatin regions. For example, the acetylation of Lys of H4 leads to a telomeric silencing (Kelly et al., 2000). In Drosophila, Lys of H4 is acetylated specifically in the... 

Thoma F, Roller T (1977) Influence of histone HI on chromatin structure. Cell 12 101-107 Thoma F, Roller T, Klug A (1979) Involvement of histone HI in the organization of the nucleosome and of the salt-dependent superstructures of chromatin. J Cell Biol 83 403 27 Turner BM, Birley AJ, Lavender J (1992) Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei. Cell 69 375-384... 

Clarkson Ml, Wells JR, Gibson F, Saint R, Tremethick DJ (1999) Regions of variant histone His2AvD required for Drosophila development. Nature 399 694-697 Costanzi C, Pehrson IR (1998) Histone macroH2Al is concentrated in the inactive X chromosome of female mammals. Nature 393 599-601... 

Heun P, Erhardt S, Blower MD, Weiss S, Skora AD, Karpen GH (2006) Mislocalization of the Drosophila centromere-specific histone CiD promotes formation of functional ectopic kinetochores. Dev Cell 10 303-315... 

Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403 41-45 Suto RK, Clarkson MJ, Tremethick DJ, Luger K (2000) Crystal structure of a nucleosome core particle containing the variant histone H2A.Z. Nature Struct. Biol. 7 1121-1124 Swaminathan J, Baxter EM, Corces VG (2005) The role of histone H2Av variant replacement and histone H4 acetylation in the establishment of Drosophila heterochromatin. Genes Dev 19 65-76... 

Histone Yeast Drosophila Mammals Function Deposition... 

Figure 1. Variants of the histones H3 from yeast Saccharomyces cerevisiae S.c.), fruit fly Drosophila melanogaster D.m), and human Homo sapiens H.s.). H3.1 is identical to H3.2 with the exception of a serine to cysteine exchange (top). H3.3 differs from H3.1/H3.2 only in four amino acid positions. Centromer-specific histones (CenH3 s) have an amino terminus of variable length (between 20 and 200 residues). They also possess an extended loop 1 region in the histone fold domain...

More recent studies in Drosophila revealed that H3.3 also plays an important role in the male pronucleus after fertilization (Loppin et al. 2005). The loss of the H3.3 chaperone HIRA impairs the replacement of paternal non-histone proteins from the sperm nucleus with maternally provided histones including H3.3, while the maternal genome exclusively contains the canonical H3. Thus, H3.3 and its deposition factor HIRA function in early fertilization events and might have a role in imprinting in higher eukaryotes. 

HD In Drosophila models of Huntington s disease, the HDAC inhibitors SAHA and sodium butyrate arrest the progressive neuronal degeneration and lethality (Steffan et al, 2001). SAHA and sodium butyrate have also been demonstrated to extend survival, ameliorate motor deficits and delay characteristic neuropathology in the mouse Huntington s disease model, R6/2 (Ferrante et al, 2003 Hockly et al, 2003). In NaBu-treated animals, animals displayed enhanced acetylation status of histones and pro-survival transcription factors like Spl and reduction in several neuropatho-logical hallmarks like striatal neuronal atrophy (Ferrante et al, 2003). Consistent with the idea that HDAC inhibition relieves transcriptional repression and that protection is downstream of mutant htt, neither SAHA nor sodium butyrate decreased mutant htt expression or aggregates (Ferrante et al, 2003 Hockly et al, 2003). 

Balasubramanyam K, Swaminathan V, Ranganathan A, Kundu TK (2003) Small molecule modulators of histone acetyltransferase p300. J Biol Chem 278(21) 19134-19140 Barlow AL, van Drunen CM, Johnson CA, Tweedie S, Bird A, Turner BM (2001) dSIR2 and dHDAC6 two novel, inhibitor-resistant deacetylases in Drosophila melanogaster. Exp Cell Res 265(1) 90-103... 

Figure 2. Current view of post-translational histone phosphorylation. Red flag mammahan specific or common, Blue flag Drosophila melanogaster specific, Black flag Saccharomyces cerevisiae specific. (See Colour Plate 18.)...

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