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:The Sc2.0 project is building a eukaryotic synthetic genome from scratch. A major milestone has been achieved with all individual Sc2.0 chromosomes assembled. Here, we describe consolidation of multiple synthetic chromosomes using advanced endoreduplication intercrossing with tRNA expression cassettes to generate a strain with 6.5 synthetic chromosomes. The 3D chromosome organization and transcript isoform profiles were evaluated using Hi-C and long-read direct RNA sequencing. We developed CRISPR Directed Biallelic URA3-assisted Genome Scan, or “CRISPR D-BUGS”, to map phenotypic variants caused by specific designer modifications, known as “bugs”. We first fine-mapped a bug in synthetic chromosome II (synII), and then discovered a combinatorial interaction associated with synIII and synX, revealing an unexpected genetic interaction that links transcriptional regulation, inositol metabolism and tRNASerCGA abundance. Finally, to expedite consolidation, we employed chromosome substitution to incorporate the largest chromosome (synIV), thereby consolidating >50% of the Sc2.0 genome in one strain.
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.
Project description:The integration of the results of QTL fine-mapping with microarray expression data offers a promising tool for understanding the genetic mechanisms influencing complex traits as fatty acid composition in pigs. The expression level of each probe may be treated as a quantitative trait and the marker genotypes used to map loci with regulatory effect on the gene expression level (eQTL) According to our previous linkage results, we carry out an eQTL scan focused on chromosomal regions showing tissue-consistent effects on fatty acids with Longissimus dorsi gene expression data in order to detect potentional candidate genes underlying the QTL previously detected. 102 IberianxLandrace backcross pigs were selected for RNA extraction and hybridization on Affymetrix microarrays. An eQTL scan was carried out with the data of 470 probes of the microarray taking into account they were related with fatty acid metabolism