High impact information on H2afy

• Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals [1].
• Therefore, targeting of macroH2A1 to the centrosome is likely part of a degradation pathway, a mechanism common to a variety of other chromatin proteins [2].
• To better understand the association of macroH2A1 with the centrosome and the formation of an MCB, we investigated the distribution of macroH2A1 throughout the somatic cell cycle [2].
• The centrosomal pool of macroH2A1 accumulates in the presence of an inhibitor of the 20S proteasome [2].
• Upon differentiation of female ES cells, Xist RNA expression became upregulated and monoallelic as judged by fluorescent in situ hybridization, but early Xist signals lacked associated macroH2A1 [3].

Biological context of H2afy

• In order to investigate the roles of M31 and macroH2A1.2 in meiosis in greater detail, we have examined their localisation patterns in surface-spread meiocytes from male and female mice [4].
• 2. Previous analyses of M31 and macroH2A1.2 localisation in mouse testis sections have indicated that both proteins are components of meiotic centromeric heterochromatin and of the sex body, the transcriptionally inactive domain of the X and Y chromosomes [4].
• Localisation of histone macroH2A1.2 to the XY-body is not a response to the presence of asynapsed chromosome axes [5].
• Histone macroH2A1.2 and the murine heterochromatin protein 1, HP1 beta, have both been implicated in meiotic sex chromosome inactivation (MSCI) and the formation of the XY-body in male meiosis [5].
• The timing of macroH2A1.2 accumulation on the Xi suggests it is not necessary for the initiation or propagation of random X-inactivation [6].

Anatomical context of H2afy

• MacroH2A1.2 and HP1 beta co-localise to autosomal pericentromeric heterochromatin in spermatocytes [5].
• In order to get a closer insight into the function of histone macroH2A1.2 we have investigated the localisation of macroH2A1.2 in surface spread spermatocytes from normal male mice and in oocytes of XX and XYTdym1 mice [5].
• Xist expression and macroH2A1.2 localisation in mouse primordial and pluripotent embryonic germ cells [7].
• Of the changes that are known to happen during X inactivation in preimplantation embryos, the accumulation of macroH2A1 appears to be the earliest marker of the inactive X chromosome and is the only change that has been shown to occur during the period when transcriptional silencing is initiated [8].
• Centrosomal association of histone macroH2A1.2 in embryonic stem cells and somatic cells [9].

Associations of H2afy with chemical compounds

• Retention of macroH2A1 at centrosomes was partially labile in the presence of nocodazole suggesting that intact microtubules are necessary for accumulation of macroH2A1 at centrosomes [3].

Co-localisations of H2afy

• Like macroH2A1, macroH2A2 forms a Macro Chromatin Body in the nuclei of female cells which is coincident with an X chromosome and co-localizes with macroH2A1 [10].

Other interactions of H2afy

• M31 and macroH2A1.2 colocalise at the pseudoautosomal region during mouse meiosis [4].
• Our results define a sequence for the loading of macroH2A1 on the Xi and place this event in the context of differentiation and Xist expression [3].
• We have now cloned a second macroH2A gene, encoding macroH2A2 which shares 80% amino acid identity with macroH2A1 [10].

Analytical, diagnostic and therapeutic context of H2afy

• We have established the timing of macroH2A1.2 association with the Xi relative to the onset of X-inactivation in differentiating murine embryonic stem (ES) cells using immuno-RNA fluorescence in situ hybridization (FISH) [6].
• Cell fractionation experiments confirmed that macroH2A1 resides at a pericentrosomal location in close proximity to the known centrosomal proteins gamma-tubulin and Skp1 [3].
• 2. We show by immunofluorescence on mouse tissue sections that MACROH2A2, like MACROH2A1.2, is concentrated in the inactive X chromosome [11].
• Using a novel thiol affinity chromatography approach to purify macroH2A1-containing chromatin fragments, we examined the distribution of macroH2A1 histone variants in mouse liver chromatin [12].
• By indirect immunofluorescence we detect macroH2A1.2 protein in a juxtanuclear structure that duplicates once per cell cycle and colocalizes with centrosomal gamma-tubulin in both XX and XY ES cells prior to and throughout their differentiation [9].

References