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Profiling the landscape of transcription and chromatin conformation reveals regulatory mechanisms involved in immune and metabolic functions

Abstract : Functional annotation of livestock genomes is a critical and obvious next step to derive maximum benefit for agriculture, animal science, animal welfare and human health. The aim of the Fr-AgENCODE project is to generate multi-species functional genome annotations by applying high-throughput molecular assays on three target tissues/cells relevant to the study of immune and metabolic traits. Here we present on-going results on gene expression and chromatin conformation in hepatocytes and CD3+CD4+ (“CD4”) and CD3+CD8+ (“CD8”) T cells with a focus on the pig species (two male and two female Large White adult pigs). These samples were processed by strand-oriented RNA-seq and ATAC-seq experiments. Principal Component Analyses on log-transformed TMM-normalized read counts in genes (from RNA-seq) and regions of chromatin accessibility (from ATAC-seq) consistently highlighted the variability between liver and the T cells, and to a lesser extent within T cells (CD4 vs. CD8), as well as between the male and female samples. Comparative analyses identified differentially expressed genes between cell types as well as potential regulatory sites from differentially accessible chromatin regions. As expected, ontology annotations of differentially expressed genes were enriched for either immunity- or metabolism-related terms. Interestingly, correlations between gene expression and promoter accessibility across samples were enriched for both extreme positive and negative values, which suggests that ATAC-seq can efficiently capture distinct regulatory mechanisms of gene expression. Candidate enhancers and repressors were identified by comparing ATAC-seq regions with predicted binding sites of 500+ transcription factors. By integrating these results with those from Hi-C chromosome conformation capture on the liver samples, we investigated differences between “active” and “repressed” topological domains in terms of functional features, including gene density and general chromatin accessibility. Altogether, these results lead to a better understanding of the molecular mechanisms involved in pig immune and metabolic functions, and illustrate a useful contribution to the functional annotation effort of the FAANG initiative.
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Conference papers
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https://hal.archives-ouvertes.fr/hal-01603057
Contributor : Archive Ouverte Prodinra <>
Submitted on : Monday, October 2, 2017 - 7:32:02 PM
Last modification on : Friday, February 26, 2021 - 11:00:02 AM

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  • HAL Id : hal-01603057, version 1
  • PRODINRA : 401608

Citation

Sylvain Foissac, Sarah Djebali Quelen, Hervé Acloque, Marie-Helene Pinard - van der Laan, Sandrine Lagarrigue, et al.. Profiling the landscape of transcription and chromatin conformation reveals regulatory mechanisms involved in immune and metabolic functions. 3. Journée de Séminaires du Département Phase sur l'Epigénétique EpiPhase, May 2017, Jouy-en-Josas, France. ⟨hal-01603057⟩

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