Project description:Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a key risk factor for coronary artery disease (CAD). The pathogenesis of CAD is multifactorial, driven by heritable and lifestyle-related risk factors. Although CD4+ T cells are one of the main cell types in atherosclerotic lesions, their interaction with atherogenic oxidised LDL (ox-LDL) remains poorly understood. Therefore, we sought to characterise the transcriptomic and epigenomic consequences of ox-LDL on CD4+ T cells. We find that ox-LDL causes a shift towards a pro-inflammatory, cytokine-producing CD4+ T cell transcriptomic state. Concurrently, ox-LDL induces genome-wide changes in chromatin accessibility, notably in promoter regions. Multiomic data integration identifies a likely role for NRF1 and SP1 transcription factors in mediating ox-LDL-induced changes in gene expression. In contrast, the influence of AP-1 related factors over CD4+ T cell gene expression decreases following ox-LDL stimulation. We leveraged our multiomic data to investigate the disease-relevance of ox-LDL exposure, by investigating genomic locations where CAD-associated single nucleotide polymorphisms were found within dynamic ox-LDL-regulated accessible chromatin regions. Together, we demonstrate a disease-relevant role for ox-LDL in atherogenic conditioning of CD4+ T cells. Understanding such cell-type specific interactions with CAD risk factors may facilitate the development of targeted therapies for CAD.
Project description:Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a key risk factor for coronary artery disease (CAD). The pathogenesis of CAD is multifactorial, driven by heritable and lifestyle-related risk factors. Although CD4+ T cells are one of the main cell types in atherosclerotic lesions, their interaction with atherogenic oxidised LDL (ox-LDL) remains poorly understood. Therefore, we sought to characterise the transcriptomic and epigenomic consequences of ox-LDL on CD4+ T cells. We find that ox-LDL causes a shift towards a pro-inflammatory, cytokine-producing CD4+ T cell transcriptomic state. Concurrently, ox-LDL induces genome-wide changes in chromatin accessibility, notably in promoter regions. Multiomic data integration identifies a likely role for NRF1 and SP1 transcription factors in mediating ox-LDL-induced changes in gene expression. In contrast, the influence of AP-1 related factors over CD4+ T cell gene expression decreases following ox-LDL stimulation. We leveraged our multiomic data to investigate the disease-relevance of ox-LDL exposure, by investigating genomic locations where CAD-associated single nucleotide polymorphisms were found within dynamic ox-LDL-regulated accessible chromatin regions. Together, we demonstrate a disease-relevant role for ox-LDL in atherogenic conditioning of CD4+ T cells. Understanding such cell-type specific interactions with CAD risk factors may facilitate the development of targeted therapies for CAD.
Project description:We present here genome-wide H3K9 acetylation data in Arabidopsis thaliana plants overexpressing TPR1 (Topless-related 1) -GFP driven by its native promoter (TPR1-OX). We compared the H3K9 acetylation of the TPR1-OX auto-immune plants in WT (Col-0) background with eds1-2 mutant background plants which do not show the auto-immune phenotype.
Project description:The tongue is a specialized muscular organ that performs multiple essential functions including mastication, deglutition, oral sensation, oral cleansing, airway maintenance and vocalization. In this study, we show Foxf1/Foxf2 serves as key mediators of hedgehog signaling in regulating myoblast migration, differentiation, and intrinsic tongue muscle organization. We took advantage of the Foxf2FLAG mice which carries 3xFLAG epitope-tagged endogenous Foxf2 protein and characterized genome-wide Foxf2 binding sites in the developing tongues using chromatin immunoprecipitation and genome sequencing (ChIP-seq). Further analyses demonstrate that Foxf1/2 transcription factors directly control the expression of Hgf, Tgfb2, and Tgfb3, to regulate tongue myogenesis.
Project description:Ecotoxicogenomics in field experiments have yielded valuable mechanistic information for organisms present in polluted environments. The Queen conch (Strombus gigas) is a threatened species and populations are declining due to anthropogenic impact that includes pollution from boating activities. In the British Virgin Islands (BVI), local Queen conch populations have exhibited imposex, a condition in which both male and female gonadal characteristics are present and studies in the BVI suggest that tributyl tin (TBT), a chemical used in boat paint, is correlated to increased incidence imposex. This present study utilized a previously validated 8 x 15K Queen conch microarray to characterize the response of the ovarian transcriptome in conch found in polluted environments with high TBT in the BVIs. There polluted sites, Road Harbour (RH) and Trellis Bay (TB), are harbours with high boating activity while the reference sites, Guana Island (GI) and Anegada (AN), are areas with low boating activity. Microarray analysis revealed that there were 17 transcripts with high homology to known genes that were differentially expressed in the environments with high TBT and these included 6 induced and 11 down-regulated transcripts (p<0.01). These differentially expressed transcripts included phosphoenolpyruvate carboxylase, transposase, and high-affinity phosphate transporter PT1. When considering both RH and TB together in comparison to GI, functional enrichment showed that the biological processes and molecular functions of calcium ion binding, immune response, and negative regulation of cell proliferation were over represented in the polluted sites. Gene set enrichment analysis revealed that transcripts involved in the biological processes of general metabolism, immune, lipid metabolism, and stress were affected in polluted environments. Although difficult to directly link changes at the transcriptomics level to TBT in the harbour, this analysis provides novel insight into pathways impacted in regions that experience heavy boating activity in the BVIs.