Global Dynamics of Stage-specific Transcription Factor Binding During Thymocyte Development

Overview

Journal Sci Rep

Specialty Science

Date 2018 Apr 6

PMID 29618724

Citations 13

Authors

Tomonori Hosoya

Ricardo DOliveira Albanus

John Hensley

Greggory Myers

Yasuhiro Kyono

Jacob Kitzman

Stephen C J Parker

James Douglas Engel

Affiliations

Soon will be listed here.

Abstract

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.

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