Regulatory T (Treg) cells are critical for tolerance to self-antigens and preventing autoimmunity. Their differentiation and function are controlled by transcription factor Foxp3, but mechanistic understanding of Foxp3 role remains elusive. Using functional genomic analysis, we explored Foxp3 function and its interaction with a highly expressed closely related factor Foxp1. We are now studying the role of Foxp3 and other factors in chromatin organization and gene expression regulation in functionally heterogeneous Treg cells across tissues.