Disease relevance of Cbx1

• In order to investigate the role of the murine HP1-like protein M31 in heterochromatin formation and gene silencing, recombinant CSD was overexpressed in Escherichia coli and crystallized using the hanging-drop vapour-diffusion method with PEG 4000 as precipitant [1].
• Apc(Min) mice have provided an example of a locus (Modifier of Min1; Mom1) modifying adenoma numbers in the intestines of inbred strains [2].

High impact information on Cbx1

• This gene, Mom-1 (Modifier of Min-1), maps to distal chromosome 4 and controls about 50% of genetic variation in tumor number in two intraspecific backcrosses [3].
• Foxl1 is a mesenchymal Modifier of Min in carcinogenesis of stomach and colon [4].
• We now report the identification of a second Modifier of Min 2 (Mom2) locus that is the result of a spontaneous mutation [5].
• Here we demonstrate that human HIPK2 is small ubiquitin-related modifier-1 (SUMO-1)-modified in vitro and in vivo at lysine residue 25, a SUMO consensus modification motif conserved in human and mouse HIPK family proteins [6].
• Thus, both MOD-1 null malic enzyme mRNAs contain the duplication deduced from cDNA sequence analyses [7].

Biological context of Cbx1

• 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 [8].
• 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 [8].
• Using this motif, termed chromo box, we have cloned a mouse candidate modifier gene, M31, that also shows considerable sequence homology to Drosophila HP1 [9].
• 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 [10].
• Maternal provision of M31 transcripts may reflect a need for M31 in the formation of a functional centromere in order that there is proper segregation of chromosomes during the early cleavage divisions; studies in fission yeast and Drosophila have suggested a crucial role for HP1-like genes in centromere function [11].

Anatomical context of Cbx1

• MacroH2A1.2 and HP1 beta co-localise to autosomal pericentromeric heterochromatin in spermatocytes [10].
• Western immunoblot analysis disclosed that MOD-1 null liver cytosol contains an 82-kDa protein that is recognized by anti-malic enzyme antibodies [7].

Associations of Cbx1 with chemical compounds

• MOD-1 enzyme activity levels were normal in the three ENU-induced mutants with altered electrophoretic mobility [12].

Other interactions of Cbx1

• The HP1 class of chromobox (Cbx) genes encode an evolutionarily conserved family of proteins involved in the packaging of chromosomal domains into a repressive heterochromatic state [13].
• M31 and macroH2A1.2 colocalise at the pseudoautosomal region during mouse meiosis [8].

Analytical, diagnostic and therapeutic context of Cbx1

• Crystallization and preliminary crystallographic studies on the chromo shadow domain (CSD) of mouse heterochromatin protein M31 [1].
• PCR products that represent M31 transcripts were detected at the one-cell stage and were maternal in origin [11].
• To decrease gene silencing, the chromo domain (CD) in the M31 (the main HP1 in mouse) was deleted by site-directed mutagenesis [14].

References