@article{TEXTUAL,
      recid = {9268},
      author = {Pacis, Alain and Mailhot-Léonard, Florence and Tailleux,  Ludovic and Randolph, Haley E. and Yotova, Vania and  Dumaine, Anne and Grenier, Jean-Christophe and Barreiro,  Luis B.},
      title = {Gene activation precedes DNA demethylation in response to  infection in human dendritic cells},
      journal = {PNAS},
      address = {2019-03-18},
      number = {TEXTUAL},
      abstract = {DNA methylation is considered to be a relatively stable  epigenetic mark. However, a growing body of evidence  indicates that DNA methylation levels can change rapidly;  for example, in innate immune cells facing an infectious  agent. Nevertheless, the causal relationship between  changes in DNA methylation and gene expression during  infection remains to be elucidated. Here, we generated  time-course data on DNA methylation, gene expression, and  chromatin accessibility patterns during infection of human  dendritic cells with Mycobacterium tuberculosis. We found  that the immune response to infection is accompanied by  active demethylation of thousands of CpG sites overlapping  distal enhancer elements. However, virtually all changes in  gene expression in response to infection occur before  detectable changes in DNA methylation, indicating that the  observed losses in methylation are a downstream consequence  of transcriptional activation. Footprinting analysis  revealed that immune-related transcription factors (TFs),  such as NF-κB/Rel, are recruited to enhancer elements  before the observed losses in methylation, suggesting that  DNA demethylation is mediated by TF binding to cis-acting  elements. Collectively, our results show that DNA  demethylation plays a limited role to the establishment of  the core regulatory program engaged upon infection.},
      url = {http://knowledge.uchicago.edu/record/9268},
}