Phosphorylation histones

Histone phosphorylation was first reported in 1966 [1,2]. The four core histones, histone variants, and HI histones are phosphorylated, with the sites of phosphorylation being found in both the amino-terminal and carboxy-terminal portions of the histones [3] (Figs. 1 and 2). Phosphorylation of the core histones has been implicated in transcription, replication, chromosome condensation, and DNA repair. 

Cell cycle studies of histone phosphorylation using synchronized Chinese hamster ovary cells and HeLa S-3 cells demonstrated that HI and H3 are phosphorylated at different times during the cell cycle, while H2A and H4 are phosphorylated at uniform rates throughout the cell cycle [4—6]. Kinetic studies of the phosphorylation of H2A and H4 in trout testis indicate that these histones are phosphorylated shortly after synthesis [7]. Phosphorylation of H4 did not occur appreciably until after a series of acetylation and deacetylation events, while H2A was phosphorylated shortly after synthesis followed by dephosphorylation. 

and H2A.X are phosphorylated at serine residue 1 [8,9]. H2A.Z is not phosphorylated. In vitro protein kinase C phosphorylates H2A at serine residue 1 [10]. Telrahymena H2A is phosphorylated in the C-terminal sequence [11]. Tetrahymena H2A.1 is phosphorylated at serine residues 122, 124, and 129, while H2A.2 is modified at serine residues 122 and 128 (Fig. 3). Phosphorylation of H2A occurs in the transcriptionally active macronucleus of Tetrahymena thermophila, but not in the transcriptionally inert micronucleus [12]. Tetrahymena H2A variant hvl is phosphorylated [13]. H4, like H2A, is phosphorylated at N-terminal serine 

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Histone phosphorylation is a common posttranslational modification fond in histones, primarily on the N-terminal tails. Phosphorylation sites include serine and threonine residues, tyrosine phosphorylation has not been observed so far. Some phosphorylation events occur locally whereas others occur globally throughout all chromosomes during specific events like mitosis. Histone phosphorylation is catalyzed by kinases. Removal of the phosphoryl groups is catalyzed by phosphatases. 

Histone Acetylation Histone Deacetylases Histone Methylation Histone Phosphorylation Histone Tails Hrv... 

ROLE OF HISTONE PHOSPHORYLATION IN CHROMATIN DYNAMICS AND ITS IMPLICATIONS IN DISEASES... 

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.)...

Table 1. Current view of histone phosphorylation sites and specific kinases...

SI39 (for mammals). The responsible kinases are members from phosphatidyli-nositol 3-kinase (PI3K)-like family kinases, which include ataxia telangiectasia mutated (ATM), AT-related (ATR), and DNA dependent protein kinase (DNA-PK) (Burma et al, 2001 Stiff et al, 2004 van Attikum and Gasser, 2005). Histone H2AX phosphorylation is directly related to repair of damaged chromatin (for details see chapter on Role of histone phosphorylation in chromatin dynamics and its implication in diseases ). 

The potential substrates for histone phosphorylation include N-terminal serine and threonine hydroxyl groups of H2A, H3, and H4 the N- and C-terminal tails of HI and the unique C-terminal of H2AX [19,29] (see Fig. 6). Similar to acetylation, phosphorylation appears to be a dynamic modification that transduces on/off signals to nuclear modulators. Enzymes implicated in regulating this pathway include the cyclin-dependent kinases and mitogen activated protein kinases, and the antagonistic phosphatase 1 [158,159]. 

Wang, Y., Zhang, W., Jin, Y., Johansen, J., and Johansen, K.M. (2001) The JIL-1 tandem kinase mediates histone phosphorylation and is required for maintenance of chromatin structure in Drosophila. Cell 105, 433-443. 

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