Project description:Additional sequencing coverage for the study by Jolma et al 2013, “DNA-binding specificities of human Transcription factors. This new deeper sequencing data has been used in the publication "Transcription factor family‐specific DNA shape readout revealed by quantitative specificity models”
Project description:Intracellular pH (pHi) dynamics regulates diverse cell processes such as proliferation, dysplasia, and differentiation, often mediated by the protonation state of a functionally critical histidine residue in endogenous pH sensing proteins. How pHi dynamics can directly regulate gene expression and whether transcription factors can function as pH sensors has received limited attention. We tested the prediction that transcription factors with a histidine in their DNA binding domain (DBD) that forms hydrogen bonds with nucleotides can have pH-regulated activity, which is relevant to more than 85 transcription factors in distinct families, including FOX, KLF, SOX and MITF/Myc. Focusing on FOX family transcription factors, we used unbiased SELEX-seq to identify pH-dependent DNA binding motif preferences, then confirm pH-regulated binding affinities for FOXC2, FOXM1, and FOXN1 to a canonical FkhP DNA motif that are 2.5 to 7.5 greater at pH 7.0 compared with pH 7.5. For FOXC2, we also find greater activity for an FkhP motif at lower pHi in cells and that pH-regulated binding and activity are dependent on a conserved histidine (His122) in the DBD. RNA-seq with FOXC2 also reveals pH-dependent differences in enriched promoter motifs. Our findings identify pH-regulated transcription factor-DNA binding selectivity with relevance to how pHi dynamics can regulate gene expression for myriad cell behaviours.
Project description:Adaptive response to stress involves an extensive reprogramming of gene expression. Under stressful conditions, the induction of efficient changes in mRNA production is crucial for maximized plant survival. Transcription and pre-mRNA processing are two closely related steps in mRNA biogenesis, yet how they are controlled in plant stress response remains elusive. Here, we show that the Arabidopsis nuclear cap-binding complex (CBC) component CBP20 directly interacts with ELF7, a subunit of the transcription elongation factor RNA Pol II-associated factor 1 complex (PAF1c) to promote RNA Pol II transcription in plant response to salt stress. CBP20 and ELF7 co-regulate the expression of a large number of genes including those crucial for salt tolerance. Both CBP20 and ELF7 are required for enhanced RNA Pol II elongation at salt-activated genes. Though CBP20 also regulates intron splicing, this function is largely independent of ELF7. Our study reveals the function of an RNA processing regulator CBC in assisting efficient RNA Pol II transcription and pinpoints the complex roles of CBC on mRNA production in plant salt stress resistance.
Project description:The sequence specificity of DNA-binding proteins is the primary mechanism by which the cell recognizes genomic features. Here, we describe systematic determination of yeast transcription factor DNA-binding specificities. We obtained binding specificities for 112 DNA-binding proteins representing 19 distinct structural classes. One-third of the binding specificities have not been previously reported. Several binding sequences have striking genomic distributions relative to transcription start sites, supporting their biological relevance and suggesting a role in promoter architecture. Among these are Rsc3 binding sequences, containing the core CGCG, which are found preferentially ~100 bp upstream of transcription start sites. Mutation of RSC3 results in a dramatic increase in nucleosome occupancy in hundreds of proximal promoters containing a Rsc3 binding element, but has little impact on promoters lacking Rsc3 binding sequences, indicating that Rsc3 plays a broad role in targeting nucleosome exclusion at yeast promoters. Keywords: Protein binding microarrays, DNA, proteins
2008-12-26 | GSE12349 | GEO
Project description:SMiLe-seq specificities of transcription factors