GATA1 mutations in benign hematologic disorders often affect the function of N-terminal zinc finger. (A) The normal function of the N-finger is to bind DNA at complex GATA motifs and to recruit FOG1; together, GATA1 and FOG1 drive expression of numerous red cell and megakaryocyte (Mk) genes. (B) Mutations in the FOG1-binding face of GATA1 disrupt the protein-protein interaction and diminish the expression of target genes. (C) Mutations in the N-finger that reduce the affinity of GATA1 for DNA also suppress expression of GATA1 target genes. (D) Structural representation of mutants in the GATA1 N-finger (magenta). Residues that are mutated in these disorders are indicated as spheres. The positions of FOG1 (yellow, derived from the structure of the GATA1:FOG1 structure¹¹¹ ) and DNA (gray, inferred from the structure of the GATA1-DNA complex¹¹² ) are shown. The NMR structure of the N-finger of GATA1 confirms the localization of the mutations to the FOG-interacting (left) or DNA binding surface (right).