Disease relevance of TTTY6B

• Genes at the centromeric end of the human leukocyte antigen region influence adaptive autoimmune diseases and cancer [1].
• Anti-endothelial cell antibodies from patients with limited cutaneous systemic sclerosis bind to centromeric protein B (CENP-B) [2].
• PATIENTS: By means of the fluorescence in situ hybridization technique with centromeric probes for chromosomes X and 11, we analyzed 40 randomly selected patients before treatment for T1 to T4 head and neck squamous cell carcinoma [3].
• Results: In four tumors with histologic features of chromophobe renal cell carcinoma (ChRCC), interphase FISH was performed using centromeric probes for chromosomes 1, 2, 6, 10, 12, 17 and 21 [4].

Psychiatry related information on TTTY6B

• 3. We propose that deletions of the FZD4 gene located within the centromeric segment cause retinal dysgenesis, while deletions within the telomeric segment account for dysmorphic craniofacial features, growth and mental retardation, and mild digital anomalies [5].

High impact information on TTTY6B

• C-terminal PTEN mutants disrupt the association of PTEN with centromeres and cause centromeric instability [6].
• PICH-positive threads connect sister kinetochores and are dependent on tension, sensitive to DNase, and exacerbated in response to premature loss of cohesins or inhibition of topoisomerase II, suggesting that they represent stretched centromeric chromatin [7].
• The centromeric DNA of each chromosome is linked to microtubule plus-ends by eight structural-protein complexes [8].
• The recent elucidation of structures of the ParB plasmid segregation protein bound to centromeric DNA, and of the tertiary structures of other segregation proteins, are key milestones in the path to deciphering the molecular basis of bacterial DNA segregation [9].
• The Aurora kinase Ipl1 maintains the centromeric localization of PP2A to protect cohesin during meiosis [10].

Biological context of TTTY6B

• Kinetochores (KTs) assemble on centromeric DNA, bi-orient paired sister chromatids on spindle microtubules (MTs) and control cell-cycle progression via the spindle assembly checkpoint [11].
• In the absence of Ipl1, Rts1 can initially bind to centromeric regions but disappears from these regions after anaphase I onset [10].
• Genes <10 kb from the CentO satellite array were expressed in several rice tissues and displayed histone modification patterns consistent with euchromatin, suggesting that rice centromeric chromatin accommodates normal gene expression [12].
• We mapped the genetic influences for type 1 diabetes (T1D), using 2,360 single-nucleotide polymorphism (SNP) markers in the 4.4-Mb human major histocompatibility complex (MHC) locus and the adjacent 493 kb centromeric to the MHC, initially in a survey of 363 Swedish T1D cases and controls [13].
• The only DNA found well within the Barr body and XIST RNA territory was centromeric and Cot-1 DNA; hence, the core of the X chromosome essentially excludes genes and is composed primarily of noncoding repeat-rich DNA [14].

Anatomical context of TTTY6B

• GCH1-HACs in every ES cell line and globin-HACs in most ES cell lines maintained their structures without detectable rearrangement or acquisition of mouse genomic DNA except one globin-HAC in an ES cell line rearranged and acquired mouse-type centromeric sequences and long telomeres [15].
• We have recently demonstrated that heterochromatin HP1 proteins are aberrantly distributed in lymphocytes of patients with immunodeficiency, centromeric instability and facial dysmorphy (ICF) syndrome [16].
• The BACH2 gene was located closer to the centromeric heterochromatin in BV173 and K562 cells as compared to NAMALWA cells [17].
• The use of centromeric signals allows the identification of two further endpoints, representing two alternative pathways of chromosome loss, i.e., impaired chromosome migration, leading to increased C1+MN frequency, and centrosome amplification, possibly leading to Cx+MN with two or more centromeric signals [18].
• The MHC class I chain-related gene A (MICA), located centromeric of HLA-B, is involved in the innate and adaptive immune response through activation of NK and T cells [19].

Associations of TTTY6B with chemical compounds

• We analyzed DNA methylation in TRAMP and found that global levels of 5-methyl-2'-deoxycytidine are unaltered, whereas specific tumors display centromeric repeat hypomethylation [20].
• We show that inhibition of the Survivin-Crm1 interaction by treatment with leptomycin B or by RNA-interference-mediated Crm1 depletion prevents centromeric targeting of Survivin [21].
• FISH utilized the LAVysion probe set (Abbott Molecular; Des Plaines, IL), which contains locus-specific probes to 5p15, 7p12 (EGFR), 8q24 (C-MYC), and a centromeric probe to chromosome 6 [22].
• Biotin-tag affinity purification of a centromeric nucleosome assembly complex [23].

Analytical, diagnostic and therapeutic context of TTTY6B

• Using a DNA fiber-fluorescence in situ hybridization approach, we demonstrated that the centromere of chromosome 3 (Cen3) contains approximately 441 kb of the centromeric satellite repeat CentO [12].
• Following new DNA extraction, molecular analysis was repeated and, in conjunction with fluorescent in situ hybridization (FISH) analysis using the Y centromeric specific probe Yc-2, confirmed the initial positive DNA findings [24].
• METHODS: To establish PGD for HS-RDEB, we designed and optimised a sensitive single cell semi-duplex polymerase chain reaction (PCR) assay for two highly polymorphic dinucleotide repeat microsatellite markers, D3S1581 (telomeric) and D3S1289 (centromeric), close to the COL7A1 gene [25].
• We used chromatin immunoprecipitation with antibodies to RNA polymerase II (RNAPol-ChIP) to test for transcription of the following repeat arrays in human cells: subtelomeric D4Z4, pericentromeric satellite 2, and centromeric satellite alpha [26].

References