Project description:Evolutionarily conserved SCAN domain-containing zinc finger transcription factors (ZSCAN) have been found in both the mouse and human genomes. Of which, Zscan4 is crucial for zygotic genome activation (ZGA) in preimplantation embryos, and induced pluripotent stem cell (iPSC) reprogramming. However, little is known about the mechanism of Zscan4 underlying these processes of cell fate control. Here we show that Zscan4f, a representative of ZSCAN proteins, is able to recruit Tet2 through its SCAN domain. The Zscan4f-Tet2 interaction promotes DNA demethylation and regulates the expression of target genes, particularly those encoding glycolytic enzymes and proteasome subunits. Disruption of the Zscan4f-Tet2 interaction impairs cellular metabolism, proteasome function, and ultimately compromises iPSC generation. These results identify Tet2 as a major cooperator for the function of Zscan4f, and suggest a common mechanism shared by SCAN family transcription factors to recruit TET DNA dioxygenases to regulate diverse cellular processes.
Project description:Genome-wide DNA methylation profiles for 82 triple negative breast cancer (TNBC) samples from the Swedsh Cancerome Analysis Network - Breast (SCAN-B) cohort.
Project description:Genome-wide DNA methylation profiles for 154 triple negative breast cancer (TNBC) samples from the Swedsh Cancerome Analysis Network - Breast (SCAN-B) cohort.
Project description:Binding to RNA has been observed for an ever-increasing number of proteins, which often have other functions. The contributions of RNA binding to protein function are best discerned by studying “separation-of-function” mutants that hamper interaction with RNA without affecting other aspects of protein function. To design these mutants, we need precise knowledge of the residues that contribute to the affinity of the protein to its RNA ligands. Here, we present RBR-scan: a technology to simultaneously measure RNA-binding affinity of a large number of protein variants. We fused individual variants with unique peptide barcodes optimized for detection by mass spectrometry (MS), purified protein pools from single bacterial culture, and assayed proteins in parallel for RNA binding. Mutations in the MS2 coat protein known to impair RNA-binding were correctly identified, as well as a previously unreported mutant, which we validated with orthogonal biochemical methods. We used RBR-scan to discover novel RNA-binding mutants in the cancer-associated splicing regulator SRSF2. Together, our results demonstrate that RBR-scan is a powerful and scalable platform for linking RNA-binding affinity to protein sequence, offering a novel strategy to decode the functional consequences of protein–RNA interactions.
Project description:Small peptides (sPeptides), a class of biological molecules of less than 100 amio acids encoded by small open reading frames (sORFs), play important roles in multiple biological process. Here, we conducted a comprehensive study using mRNA-seq, Ribo-seq, and Mass Spectrometry (MS) on six tissues (each with at least two replicates) of maize, set up a bioinformatic pipeline, and performed a genome-wide scan of sORFs and sPeptides in maize. Our study sets up a guildline for the genome-wide scan of sORFs and sPeptides in plants by integrating Ribo-seq, and MS data, provides a more comprehensive resource of functional sPeptides in maize, and sheds light on the complex biological system of plants in a new perspective.
