Project description:These samples have been analyzed for global alternative splicing variation on exon-level expression data using the FIRMA algorithm. We have identified and described transcriptome instability as a genome-wide, pre-mRNA splicing related characteristic of solid cancers.
Project description:To reveal the role of sulfur metabolism genes in memory formation processes, transcriptome libraries were obtained from the heads of 5-day-old naive males. The libraries were generated from Drosophila strains created in our laboratory with deleted cbs genes ( CBS-/-(5) and CBS-/-(8), cse (CSE-/-) and strains with double deletion of cbs and cse genes (CBS-/-,CSE-/-(1) and (CBS-/-,CSE-/-(2). Strain 58492, in which deletions were introduced by the CRISP/CAS9 method, was used as a control strain.
Project description:Purpose: The goal of this study is to investigate the role of CBS enzyme in colorectal carcinogenesis Methods: RNA-Seq transcriptome analysis of CBS-overexpression in NCM356 cels compared to control vector cells
Project description:The multivalent binding of CTCF to a variety of DNA sequences is thought to underlie its ability to mediate a large repertoire of cellular functions. CTCF is a 11 zinc-finger (ZF) protein that is anchored to a majority of its target sites via binding to a 20 base-pair core DNA sequence. Yet the diversity of CTCF binding sites (CBS) has not fully been characterized. Here we assessed CTCF occupancy in cultured mouse cortical neurons as a function of neuronal activity and observed that ~ 22 % of CBS lack the consensus CTCF motif. We report that sequence diversity at most of these atypical CBS is not random but involves degeneracy at specific nucleotide positions within the core CTCF position weight matrix (PWM) that likely affect the binding of ZFs 6 and 7. Surprisingly, degeneracy at the same nucleotides not only define most atypical CBS, but also CBS within most gene promoters, and CBS that are dynamically altered following neuronal stimulation, revealing how atypical CTCF binding could affect gene activity. Dynamic CBS across neural differentiation and neuronal stimulation are found both within and outside loop anchors and TADs, indicating that dynamic CBS could regulate gene activity independently of loop anchoring. Finally, we identified a second mode of atypical CTCF binding that defines most tissue-specific CBS. Unlike other atypical CBS, tissue-specific CBS largely bind sequences unrelated to the core CTCF motif and are enriched within the bodies of tissue-specific genes. Overall, these results indicate how CTCF binding at atypical CBS could allow it to dynamically regulate gene activity patterns during differentiation, development, and in response to environmental cues.
Project description:The multivalent binding of CTCF to a variety of DNA sequences is thought to underlie its ability to mediate a large repertoire of cellular functions. CTCF is a 11 zinc-finger (ZF) protein that is anchored to a majority of its target sites via binding to a 20 base-pair core DNA sequence. Yet the diversity of CTCF binding sites (CBS) has not fully been characterized. Here we assessed CTCF occupancy in cultured mouse cortical neurons as a function of neuronal activity and observed that ~ 22 % of CBS lack the consensus CTCF motif. We report that sequence diversity at most of these atypical CBS is not random but involves degeneracy at specific nucleotide positions within the core CTCF position weight matrix (PWM) that likely affect the binding of ZFs 6 and 7. Surprisingly, degeneracy at the same nucleotides not only define most atypical CBS, but also CBS within most gene promoters, and CBS that are dynamically altered following neuronal stimulation, revealing how atypical CTCF binding could affect gene activity. Dynamic CBS across neural differentiation and neuronal stimulation are found both within and outside loop anchors and TADs, indicating that dynamic CBS could regulate gene activity independently of loop anchoring. Finally, we identified a second mode of atypical CTCF binding that defines most tissue-specific CBS. Unlike other atypical CBS, tissue-specific CBS largely bind sequences unrelated to the core CTCF motif and are enriched within the bodies of tissue-specific genes. Overall, these results indicate how CTCF binding at atypical CBS could allow it to dynamically regulate gene activity patterns during differentiation, development, and in response to environmental cues.
Project description:Colorectal cancer is a heterogeneous disease molecularly characterized by inherent genomic instabilities, chromosome instability and microsatellite instability. In the present study we propose transcriptome instability as an analogue to genomic instability on the transcriptome level. Exon microarray data from two independent series of altoghether 160 colorectal cancer tissue samples was used for global alternative splicing detection using the FIRMA algorithm (aroma.affymetrix). The sample-wise amounts of these alternative splicing scores exceeding a defined threshold (deviating exon usage amounts) were summarized to provide the basis for description of transcriptome instability. This characteristic was shown to be associated with splicing factor expression levels and patient survival in both independent sample series.