Disease relevance of Phc1

• Since homozygous Rae28-deficient (Rae28(-/-)) mice displayed cardiac anomalies similar to congenital heart diseases in humans, we examined the role of Rae28 in cardiac morphogenesis at the molecular level [1].
• Interestingly, however, cardiomyocyte-specific overexpression of rae28 caused dilated cardiomyopathy, which was associated with cardiomyocyte apoptosis, abnormal myofibrils, and severe heart failure [2].
• Its human homologue, RAE28, is located on chromosome 12p13, which frequently is associated with chromosomal abnormalities and loss of heterozygosity in patients with hematologic malignancies [3].
• Results suggest that Rae28/Ph1 and Ring1B dissociate from the chromatin upon its condensation in mitotic prophase in the U2-OS human osteosarcoma cell line [4].
• Scm protein also bears homology in multiple domains to a mouse protein, Rae-28 (Nomura, M., Takihara, Y. and Shimada, K. (1994) Differentiation 57,39-50) and to a fly tumor suppressor protein, the product of the lethal(3)malignant brain tumor gene (Wismar, J. et al., (1995) Mech. Dev. 53, 141-154) [5].

High impact information on Phc1

• Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells [6].
• Hematopoietic activity was impaired in the fetal liver of rae28-deficient animals (rae28-/-), as demonstrated by progressive reduction of hematopoietic progenitors of multilineages and poor expansion of colony forming units in spleen (CFU-S(12)) during embryonic development [6].
• This is the first report to suggest that rae28 has a crucial role in sustaining the activity of HSCs to maintain hematopoiesis [6].
• The genetic interactions further reveal the functional overlap between Phc2 and Phc1 and a strict dose-dependent requirement during A-P specification and embryonic survival [7].
• These results indicate that the rae28 gene is involved in the regulation of Hox gene expression and segment specification during paraxial mesoderm and neural crest development [8].

Chemical compound and disease context of Phc1

• Expression of the rae28/mph1 gene is induced during retinoic acid (RA)-mediated differentiation of embryonal carcinoma F9 cells [9].

Biological context of Phc1

• The sequences of individual oligonucleotides included the following consensus sequences; 5'-ACCA-3', 5'-ACCCA-3', 5'-CTATCA-3' and 5'-TGCC-3'. The oligonucleotides including these consensus sequences were show to have significant affinity with the GST-RAE28 fusion protein [10].
• In this study we synthesized the glutathione S transferase-RAE28 (GST-RAE28) fusion protein and examined sequence-specific DNA binding activity in the RAE28 protein by using the selected and amplified binding site method [10].
• During maturation of oocytes, significant alterations of Rae28/Ph1 and Ring1B localization are concordant with configuration changes of the chromatin at the germinal vesicle stage of meiotic prophase [4].
• Importantly, dissociation of Rae28/Ph1 and Ring1B from the chromatin temporally correlates with transcriptional arrest both in mitosis and meiosis [4].
• The overall exon-intron organization suggested that three different Rae28 mRNAs are generated through alternative splicing [11].

Anatomical context of Phc1

• Regulation of Hoxb3 expression in the hindbrain and pharyngeal arches by rae28, a member of the mammalian Polycomb group of genes [12].
• Analysis of a neural crest marker, p75, in rae28-deficient mice revealed that the neural crest cells begin to ectopically express Hoxb3 after leaving the hindbrain [12].
• In this study, we examined the role of rae28 in lymphocyte development [3].
• Because homozygous rae28-deficient (rae28-/-) mice died in the perinatal period, we examined lymphocyte development by generating chimeric mice reconstituted with green fluorescence protein-labeled mutant fetal liver cells as well as in in vitro culture systems [3].
• Furthermore, the human RAE28 locus may provide a candidate gene causing the molecular pathogenesis of childhood B-cell precursor ALL [3].

Other interactions of Phc1

• In this study, we examined the time course of Hoxb3 expression during late gastrulation and early segmentation of rae28-deficient mice [12].
• Severe B-cell maturation arrest was observed in rae28-/- between pro- and pre-B lymphocyte stages [3].
• In this study, we analyzed subcellular localization of Rae28/Ph1 and Ring1B by using newly generated monoclonal antibodies in mitotic somatic cells and meiotic mouse oocytes [4].
• Gel filtration analysis of embryonic extracts indicates that RAE28, BMI1 and M33 exist in large multimeric complexes [13].

Analytical, diagnostic and therapeutic context of Phc1

• To study the role of the rae28 gene in mouse development, we generated rae28-deficient mice by gene targeting in embryonic stem cells [8].
• Furthermore, the rae28 gene has been located on the R-positive F3 band of mouse chromosome 6 by the direct R-banding fluorescence in situ hybridization methods [11].

References