Project description:Polycystic ovary syndrome (PCOS) is a complex endocrine disorder, of which the morbidity among women aging from 18 to 44 years old can be as high as 10%. Insulin resistance is an important characteristic of PCOS and affects approximately 65-70% of women with PCOS. Our previous work identified two AR alternative splicing variants (ASVs) in human granulosa cells (hGCs), Insertion (Ins) and deletion (Del) isoforms, takes up 62% of PCOS specifically. Both isoforms display altered genome-wide recruited genes and genes expressions which are tightly associated with steroidogenesis, folliculogenesis and ovulation. However, the molecular regulatory mechanism of ASVs in hGCs of insulin resistance needs to be illustrated.
Project description:D-galactose orally intake ameliorate DNCB-induced atopic dermatitis by modulating microbiota composition and quorum sensing. The increased abundance of bacteroidetes and decreased abundance of firmicutes was confirmed. By D-galactose treatment, Bacteroides population was increased and prevotella, ruminococcus was decreased which is related to atopic dermatitis.
Project description:In mammals, DNA methylation occurs mainly at 5mC of CpG dinucleotides. The methylation on the promoter leads to the suppression of gene expression, while the functional role of gene body DNA methylation in highly expressed genes has yet to be clarified. Here, we show that the Dnmt3b-dependent intragenic DNA methylation protects the gene body from RNA Polymerase II (RNA Pol II) spurious entry and cryptic transcription initiation. Using different genome-wide approaches, we demonstrate that loss of Dnmt3b leads to an increase of the RNA Pol II engagement within gene bodies and spurious intragenic transcription initiation events. Furthermore, inhibition of RNA Pol II spurious entry depends on the enzymatic activity of the Dnmt3b recruited by H3K36me3. Thus, elongating RNA Pol II triggers an epigenetic crosstalk that involves SetD2, H3K36me3, Dnmt3b, and DNA methylation to ensure gene transcription initiation fidelity with implications for intragenic hypomethylation in cancer.
Project description:Cappable-seq was used to map transcription start sites globally in B. subtilis and E. coli to investigate spurious transcription, and how B. subtilis prevents it.
Project description:To determine whether the developmental defects of urt1-1 xrn4-3 are linked to the biogenesis of spurious siRNAs, we analyzed small RNA libraries and indeed detected the accumulation of 21 nt siRNAs originating from mRNA loci in urt1-1 xrn4-3.
Project description:We report the ChIP-seq profiling of a spurious transcriptional factor Sef1 in non-typical model yeast species, Lachancea kluyveri, and show that LkSef1 targets many TCA cycle and many others genes but has very limited regulatory effects to these target genes.
Project description:The fidelity of signal transmission requires the binding of regulatory molecules to their cognate targets. However, the crowded cell interior risks off-target interactions between proteins that are functionally unrelated. Understanding the constraints this imposes on cell systems evolution requires the fitness cost of spurious interactions to be quantified. Towards this end, we express human tyrosine kinases in the budding yeast S. cerevisiae. Yeast lacks bona fide tyrosine kinases and so the majority of resulting pY sites are functionless and artificial. We express 24 unique tyrosine kinases in total and perform phosphoproteomics in each case, resulting in ~30,000 phosphosites sites mapping to 3500 phosphoproteins. Examination of the fitness costs in each strain reveals a strong correlation between the number of spurious pY sites generated and negative effects on growth. Moreover, the prediction of pY effects on protein structure and on protein function (conservation-based) reveals potential for the widespread perturbation of the yeast proteome. Comparing the spurious pY sites (pre-selection) with native pY sites in human (post-selection) also demonstrates the recurrent modification of proteins and sites with no homology to native substrates. However, examination of these data together (fitness and phosphoproteomics) strongly suggests that a large number of the pY sites generated have a negligible effect on fitness. Finally, we test the hypothesis of pY counter-selection following the emergence of tyrosine kinases in metazoan species, but find no strong evidence for proteome-wide selection against spurious Y phosphorylation.