| Autor: |
Hosoya T; Department of Cell and Developmental Biology, Ann Arbor, USA., D'Oliveira Albanus R; Department of Computational Medicine and Bioinformatics, Ann Arbor, USA., Hensley J; Department of Computational Medicine and Bioinformatics, Ann Arbor, USA., Myers G; Department of Cell and Developmental Biology, Ann Arbor, USA., Kyono Y; Department of Computational Medicine and Bioinformatics, Ann Arbor, USA.; Department of Human Genetics, University of Michigan, 3035 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan, 48109-2200, USA., Kitzman J; Department of Computational Medicine and Bioinformatics, Ann Arbor, USA.; Department of Human Genetics, University of Michigan, 3035 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan, 48109-2200, USA., Parker SCJ; Department of Computational Medicine and Bioinformatics, Ann Arbor, USA.; Department of Human Genetics, University of Michigan, 3035 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan, 48109-2200, USA., Engel JD; Department of Cell and Developmental Biology, Ann Arbor, USA. engel@umich.edu. |
| Abstrakt: |
In vertebrates, multiple transcription factors (TFs) bind to gene regulatory elements (promoters, enhancers, and silencers) to execute developmental expression changes. ChIP experiments are often used to identify where TFs bind to regulatory elements in the genome, but the requirement of TF-specific antibodies hampers analyses of tens of TFs at multiple loci. Here we tested whether TF binding predictions using ATAC-seq can be used to infer the identity of TFs that bind to functionally validated enhancers of the Cd4, Cd8, and Gata3 genes in thymocytes. We performed ATAC-seq at four distinct stages of development in mouse thymus, probing the chromatin accessibility landscape in double negative (DN), double positive (DP), CD4 single positive (SP4) and CD8 SP (SP8) thymocytes. Integration of chromatin accessibility with TF motifs genome-wide allowed us to infer stage-specific occupied TF binding sites within known and potentially novel regulatory elements. Our results provide genome-wide stage-specific T cell open chromatin profiles, and allow the identification of candidate TFs that drive thymocyte differentiation at each developmental stage. |
