Project description:The X-chromosomal dystonia parkinsonism syndrome (XDP) is associated with sequence changes within the TAF1/DYT3 multiple transcript system. While most sequence changes are intronic, one, DSC3, is located within an exon (d4). Transcribed exon d4 occurs as part of multiple splice variants. These variants include exons d3 and d4 spliced to exons of TAF1, and an independent transcript composed of exons d2-d4. Location of DSC3 in an exon (d4) and utilization of this exon in multiple splice variants suggests an important role of DSC3 in the pathogenesis of XDP. To test this hypothesis we transfected neuroblastoma cells with four expression constructs, including exons d2-d4 (d2-d4/wild-type (wt) and d2-d4/DSC3) and d3-d4 (d3-d4/wt and d3-d4/DSC3). Expression profiling revealed a dramatic effect of DSC3 on overall gene expression. 362 genes differ between cells containing d2-d4/wt and d2-d4/DSC3. Annotation clustering revealed high enrichment of genes related to dopamine metabolism, vesicular transport, synapse function, Ca++ metabolism, and oxidative stress. 211 genes were differentially expressed in d3-d4/wt vs. d3-d4/DSC3. Annotation clustering highlighted genes in signal transduction and cell-cell interaction. The data shows an important role of physiologically occurring transcript d2-d4 in normal brain function. Interference with this role by DSC3 is a likely pathological mechanism in XDP. Disturbance of dopamine function and of Ca++ metabolism can explain abnormal movement; loss of protection against reactive oxygen species may account for the neurodegenerative changes in XDP. Although d3-d4 also affect genes potentially related to neurodegenerative processes their physiologic role as splice variants of TAF1 awaits further exploration.
Project description:The X-chromosomal dystonia parkinsonism syndrome (XDP) is associated with sequence changes within the TAF1/DYT3 multiple transcript system. While most sequence changes are intronic, one, DSC3, is located within an exon (d4). Transcribed exon d4 occurs as part of multiple splice variants. These variants include exons d3 and d4 spliced to exons of TAF1, and an independent transcript composed of exons d2-d4. Location of DSC3 in an exon (d4) and utilization of this exon in multiple splice variants suggests an important role of DSC3 in the pathogenesis of XDP. To test this hypothesis we transfected neuroblastoma cells with four expression constructs, including exons d2-d4 (d2-d4/wild-type (wt) and d2-d4/DSC3) and d3-d4 (d3-d4/wt and d3-d4/DSC3). Expression profiling revealed a dramatic effect of DSC3 on overall gene expression. 362 genes differ between cells containing d2-d4/wt and d2-d4/DSC3. Annotation clustering revealed high enrichment of genes related to dopamine metabolism, vesicular transport, synapse function, Ca++ metabolism, and oxidative stress. 211 genes were differentially expressed in d3-d4/wt vs. d3-d4/DSC3. Annotation clustering highlighted genes in signal transduction and cell-cell interaction. The data shows an important role of physiologically occurring transcript d2-d4 in normal brain function. Interference with this role by DSC3 is a likely pathological mechanism in XDP. Disturbance of dopamine function and of Ca++ metabolism can explain abnormal movement; loss of protection against reactive oxygen species may account for the neurodegenerative changes in XDP. Although d3-d4 also affect genes potentially related to neurodegenerative processes their physiologic role as splice variants of TAF1 awaits further exploration. We transfected neuroblastoma cells with four expression constructs, including exons d2-d4 (d2-d4/wild-type (wt) and d2-d4/DSC3) and d3-d4 (d3-d4/wt and d3-d4/DSC3).
Project description:We report the global occupancy by ChIP-seq of AIB1 in MCF10A, MCF10A-D4, MCFDCIS and MCFDCIS-D4 cells. We performed ChIP and library preparation with the ActiveMotif Low Cell ChIP-seq kit. Data was aligned to hg19 with rsubread, data was sorted and de-duplicated with SAMTOOLS, and peaks were called with CSAW. Analysis was done with ChIP-seeker in R.
Project description:Chip-seq for MoAtf1 in M. oryzae, bZip transcription factor MoAtf1 was previous reported that involved in the full virulence of Magnaporthe oryzae. Here, we performed of MoAtf1 chip-seq assays to uncovered the regulation network