Project description:We propose a tool named TimeReg to do Time Course Regulatory Analysis from paired gene expression and chromatin accessibility data.
Project description:This SuperSeries is composed of the following subset Series: GSE37163: Gene expression data from time course of fin regeneration in Danio rerio (part 1) GSE37164: Gene expression data from time course of fin regeneration in Danio rerio (part 2) Refer to individual Series
Project description:The ability to regenerate or recover from injuries varies greatly not only between species but also between tissues and organs or developmental stages of the same species. The mechanisms behind these different regenerative capabilities are ultimately dependent on the control of genome activity, determined by a complex interplay of regulatory elements functioning at the level of chromatin. Resetting of gene expression patterns during injury responses is, thus, shaped by the coordinated action of genomic regions (enhancers, silencers) that integrate the activity of multiple sequence-specific DNA binding proteins (transcription factors and cofactors). Using genome- wide approaches to interrogate chromatin function here we identify the regulatory elements governing tissue recovery in Drosophila wing imaginal discs, which show a high regenerative capacity after genetically induced cell death. Our findings point to a global co-regulation of gene expression and provide evidence for Damage Responding Regulatory Elements (DRRE), some of which are novel whereas others are also used in other tissues or developmental stages.
Project description:Loss-of-function mutations in genes coding for subunits of the large, multifarious BRG1/BRM associated factor (BAF) chromatin remodeling complexes are frequently causative for cancer or developmental diseases1-5. Cells lacking the most frequently mutated subunits like the ATPase SMARCA4 typically exhibit drastic chromatin accessibility changes, especially of important regulatory regions6-12. However, so far it remains unknown how these changes are established over time, and whether they are causative for intra-complex synthetic lethalities abrogating the formation (SMARCC1-SMARCC2)8,13,14 or activity (SMARCA4-SMARCA2)15-17 of BAF complexes. Here, we utilize the dTAG system18 to induce acute degradation of BAF subunits in wild-type and BAF mutant backgrounds and analyze the resulting chromatin accessibility changes with high kinetic resolution. We observe that chromatin alterations are established faster than the duration of one cell cycle and that maintaining genome accessibility requires constant ATP-dependent remodeling. Completely abolishing BAF complex function by acute degradation of a synthetic lethal subunit in a paralog-deficient background results in a near-complete loss of chromatin accessibility at BAF-controlled sites, especially at super-enhancers, providing a mechanism for intra-complex synthetic lethalities.