Pioneer Transcription Factor Batf Controls Chromatin Accessibility And Ctcf-Mediated Chromatin Architecture In Cd4+T Cells

Abstract Pioneer transcription factors are a unique class of proteins that access heterochromatin, facilitate chromatin accessibility, and recruit other transcription factors to regulate gene transcription. The basic leucine zipper transcription factor ATF-like (BATF) is a critical factor for the development of T helper cell lineages. While BATF has been proposed as a pioneer factor in both T and B cells, its molecular functions are incompletely understood. In this study, we have identified a novel aspect of the pioneer function of BATF in controlling the chromatin landscape in developing effector T cells. We find that BATF is indispensable for the recruitment of chromatin-organizing complexes containing the DNA binding factor CTCF and other co-factors such as Oct1 and Ets1 to a subset of enhancer and chromatin-looping nodes during effector T cell lineage specification. Accordingly, BATF has a unique function in modulating genomic spatial organization in a CTCF-dependent manner. This study establishes BATF as a bona fide pioneer factor and provides novel insight into its role as a spatial genome organizer that modulates chromatin accessibility and initiates chromatin looping for the coordinate and differential gene expression in CD4+ T cells.