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Networks of intergenic long-range enhancers and snpRNAs drive castration-resistant phenotype of prostate cancer and contribute to pathogenesis of multiple common human disorders Nature Precedings
Anna Glinskii; Shuang Ma; Jun Ma; Denise Grant; Chang-Uk Lim; Ian Guest; Stewart Sell; Ralph Buttyan; Gennadi Glinsky.
Biological and mechanistic relevance of intergenic disease-associated genetic loci (IDAGL) containing highly statistically significant disease-linked SNPs remains unknown. Here we present the experimental and clinical evidence revealing important role of IDAGL in human diseases. Targeted RT-PCR screen coupled with sequencing of purified PCR products detects widespread transcription at multiple intergenic disease-associated genomic loci (IDAGL) and identifies 96 small non-coding trans-regulatory RNAs of ~ 100-300 nt in length containing SNPs associated with 21 common human disorders (snpRNAs). Functionality of snpRNAs is supported by multiple independent lines of experimental evidence demonstrating their cell-type-specific expression and evolutionary...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Genetics & Genomics; Molecular Cell Biology; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/6069/version/1
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Unique for human centromeric regions of interphase chromatin homing (CENTRICH) govern dynamic features of chromatin fractal globules Nature Precedings
Gennadi Glinsky.
We report the results of the genome-wide alignment of inter- and intra-chromosomal chromatin interactions within the context of interphase chromatin binding to nuclear lamina and nucleolus. For all human chromosomes, a significant correlation exists between binding of chromosomal loci to nuclear lamina and segregation into spatially-defined distinct compartments of genome-wide chromatin interactions identified by Hi-C method. We report identification of near-centromeric intergenic regions on human chromosomes (chr2; chr10; chr17; chr1), which are highly enriched for interphase chromatin homing sites and function as attractors of long-range physical interactions (Centromeric Regions of Interphase Chromatin Homing, CENTRICH). CENTRICH are engaged in 397-1526...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Developmental Biology; Genetics & Genomics; Molecular Cell Biology; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/6756/version/1
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