Models for control of erythroid gene expression by transcription factors and cis-regulatory elements. (A-B) The same cis-regulatory element can be bound by different TFs that exert antagonistic activities, such as GATA1and GATA2. (C) The same TF, such as GATA1, can either repress or activate gene expression, and this may depend, at least in part, on the distance of the cis-regulatory element to which it binds. (D) Different TFs, such as GATA2 and GATA1, can bind distinct cis-regulatory elements and control the same gene in an antagonistic manner. (E-F) The same TF, as exemplified by GATA1, can bind the same cis-regulatory element, but can display activating effects or inhibitory effects based on the recruitment of coactivators, such as the LDB1 complex, or corepressors, such as the GFI1B/LSD1 complex. These complexes help to activate or repress gene expression through epigenetic changes. (G-H) TFs can be modulated by long-range spatial interactions, bridging 2 distal enhancers through homo- or heterotypic interactions (with CTCF for instance) in a synergistic way. Professional illustration by Somersault18:24.