Disease relevance of HIST2H2AA3

• Several studies using the mouse models also demonstrate the influence of class II molecules, especially the H2-A, which is the mouse homologue of HLA-DQ, in experimental autoimmune myasthenia gravis (EAMG) [1].
• Here, we show that treatment of T-47D-5 human breast cancer cells with actinomycin D (10 micrograms/mL) or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, inhibitors of heterogeneous nuclear RNA synthesis, selectively reduced the level of uH2B, but not uH2A, uH2A.Z, or polyubiquitinated H2A, in chromatin [2].
• We investigated histone H2A-immunoreactive proteins in acute monocytic leukemia THP-1 cells using three polyclonal antibodies raised against peptides corresponding to distinct regions of H2A [3].
• To identify parts of the enzyme that are capable of binding H2A, we expressed several deletion mutants of UbcH2 in E. coli and tested the ability of the affinity purified mutant proteins to ubiquitinate H2A in the presence of bacterial expressed E1 and ubiquitin [4].
• CONCLUSIONS: Our data suggest that AHAs in localized scleroderma are directed against native chromatin, since H1, H2A, and H2B occupy a relatively exposed portion of chromatin [5].

High impact information on HIST2H2AA3

• Although the response coincides with phosphorylation of variant histone H2AX, H2AX was not required for H2A ubiquitylation [6].
• Here we show that DNA damage induces monoubiquitylation of histone H2A in the vicinity of DNA lesions [6].
• Ultraviolet (UV)-induced monoubiquitylation of H2A is dependent on functional nucleotide excision repair and occurs after incision of the damaged strand [6].
• Together our data show that monoubiquitylation of H2A forms part of the cellular response to UV damage and suggest a role of this modification in DNA repair-induced chromatin remodeling [6].
• We propose that Ino80 and Swr1 function antagonistically at chromatin surrounding a DSB, and that they regulate the incorporation of different histone H2A variants that can either promote or block cell cycle checkpoint adaptation [7].

Biological context of HIST2H2AA3

• Evidence for a human histone gene cluster containing H2B and H2A pseudogenes [8].
• In a previous communication, we showed that the H2A.1/H2A.2 histone variant ratio decreases in a linear manner during the in vitro aging of human diploid fibroblasts [9].
• This question was examined by measuring the relative expression of seven members of the human histone H2A multigene family in four cell lines of diverse origin [10].
• We propose that picNuA4 represents a nontargeted histone H4/H2A acetyltransferase activity responsible for global acetylation, whereas the NuA4 complex is recruited to specific genomic loci to perturb locally the dynamic acetylation/deacetylation equilibrium [11].
• While no Xist RNA-interacting factors have been identified, a growing collection of chromatin alterations have been identified on the inactive X, including variant histone H2A composition and histone H3 methylation [12].

Anatomical context of HIST2H2AA3

• In addition, there were up to five-fold differences among the cell lines in the amount of the H2A mRNA species as a fraction of total RNA [10].
• An abundant complex of H2A, H2B, and Kap114p was detected in cytosol [13].
• The different late H2A and H2B mRNAs are present in as few as 200 copies in the egg and each accumulate to 3-5 X 10(5) molecules in the gastrula embryo [14].
• One of the late mRNAs, the H2A-3 mRNA, is also abundant in testis RNA and codes for the H2A variant present in sperm chromatin [14].
• Despite the fact that histone H2A ubiquitination affects about 10-15% of this histone in most eukaryotic cells, histone ubiquitination is among one of the less-well-characterized post-translational histone modifications [15].

Associations of HIST2H2AA3 with chemical compounds

• In addition to the previously described mammalian 2A variants H2A.1 and H2A.2, we describe two variants which are separable from each other and from variants 1 and 2 on both sodium dodecyl sulfate and acetic acid-urea gels [16].
• One of these encodes an H2A.2 species containing methionine [10].
• Separation of micrococcal nuclease-digested chromatin by sucrose gradient ultracentrifugation shows cofractionation of H2A-Bbd with nucleosomes, supporting the idea that H2A-Bbd is incorporated into nucleosomes as a substitute for the core histone H2A [17].
• As a result of the process of X chromosome inactivation, chromatinon the mammalian inactive X chromosome (Xi) is marked by several modifications, including histone hypoacetylation, trimethylation of lysine 9 on histone H3 (H3TrimK9) and substitution of core histone H2A with the histone variant MacroH2A [18].
• We report here that imatinib triggers GIST cell apoptosis in part through the up-regulation of soluble histone H2AX, a core histone H2A variant [19].

Analytical, diagnostic and therapeutic context of HIST2H2AA3

• Amino acid composition and partial sequence analysis indicated that the purified ovarian GnRH-BI is histone H2A [20].
• Here we used chromatin immunoprecipitation to demonstrate that MBF-1 occupies its site regardless of the transcriptional state of the H2A gene [21].
• The results of gel electrophoresis, fluorescence titration and electron microscopy showed that such a positive supercoiling was not able to release H2A-H2B, nor to unfold the nucleosome to any detectable extent [22].
• As found by gel electrophoresis, Western blotting, and liquid chromatography/mass spectrometry, histones extracted from the cells contained a new fraction of histone H2A lacking the terminal octapeptide (q-H2A) [23].
• Two unknown immunoreactive proteins (9- and 12-kDa proteins), H2A (14kDa) and ubiquitinated H2A (23kDa) were found in the cell lysates prepared by immediate direct addition of SDS-PAGE sample buffer to the cells as well as in the nuclear and chromatin fractions [3].

References