Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cells of blood and bone marrow often exhibit a genome- or ploidywise organization of the two haploid sets, representing apparently maternal and paternal chromosomes in interphase nuclei and in metaphase spreads. This provides the opportunity to perform "genomic karyotyping." Such application of karyotyping may indicate whether two chromosomes involved in a translocation are both maternal, both paternal, or intermingled, i.e., one maternal and the other paternal (we refer to this as mixed). The parental origin for these translocations likely has profound differences and implications in disease expression and response to treatments, making such information very important to personalized medicine. In this mini-review, we present our observations from specimens with translocations BCR-ABL, t(9;22) and PML-RARA, t(15;17). About 20% metaphases of these specimens indicated ploidywise organization and were amenable to genomic karyotyping analysis. Fluorescence in situ hybridization (FISH) probes for BCR-ABL translocation suggest a close approximation of the HSA 9 and 22, as control values for false-positive signals run from approximately 5-10%. Given a ploidywise distribution of the maternal and paternal sets of chromosomes, it would be expected that the chromosomes involved in the translocation t(9;22) would more often belong to one of the two genomes, either maternal or paternal. Contrastingly, HSA 15 and 17 are not considered as spatially close to each other and therefore an intragenomic involvement would be rarer for translocation t(15;17). In 14 out of the 21 (66.6%) specimens with informative metaphases, the chromosomes involved in the translocation BCR-ABL were restricted to one of the two genomes--either maternal or paternal. In cases of translocation PML-RARA only 4 out of 21 (19.1%) specimens indicated an intragenomic involvement. These simple yet informative analyses of cancer-related translocations show profound underlying genomic origins and lend support to genomic karyotyping.
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PMID:Identification of parental chromosomes involved in translocations BCR-ABL, t(9;22) and PML-RARA, t(15;17). 1918 37

Multifunctional adapter and chaperone protein Daxx participates in the regulation of a number of mainly transcription-related processes. Most notably in a complex with chromatin-remodelling ATPase ATRX, Daxx serves as a histone H3.3 chaperone at telomeric regions and certain genes. In this report we document that Daxx interacts with another chromatin-remodelling, ATPase Brg1. We confirm the Daxx-Brg1 association both in vitro and in cells and show that Daxx interacts with Brg1 in high-molecular-weight complexes. Ectopic co-expression of Daxx with Brg1 and PML could shift disperse nuclear localisation of Brg1 into PML bodies. Mapping the Daxx-Brg1 interaction revealed that Daxx preferentially binds the region between Brg1 N-terminal QLQ and HSA domains, but also weakly interacts with its C-terminal part. Brg1 interacted with both the central and N-terminal parts of Daxx. SiRNA-mediated down-regulation of Daxx in SW13 adrenal carcinoma cells markedly enhanced expression of Brg1-activated genes CD44 or SCEL, suggesting that Daxx either directly through Brg1 and/or indirectly via other factors is a negative regulator of their transcription. Our findings point to Brg1 as another chromatin-remodelling protein that might similarly, as ATRX, target Daxx to specific chromatin regions where it can carry out its chromatin- and transcription-regulating functions.
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PMID:Multifunctional adaptor protein Daxx interacts with chromatin-remodelling ATPase Brg1. 2895 30