Chromatin interactions (looping) between promoters and distal regulatory elements depend on DNA binding by transcription factors. Bailey et al. set out to identify chromatin-looping factors by comparing human genome-wide binding profiles of >70 transcription factors and found that zinc finger protein 143 (ZNF143) binds directly to RNA polymerase II-bound promoters and indirectly to CTCF- and cohesin complex-bound enhancers. Chromatin conformation capture data revealed that ZNF143 preferentially binds regions of chromatin interactions between promoters and distal elements, including those that are lineage- and cell type-specific. Depleting ZNF143 decreased the interactions between two examined genes and their distal elements, and resulted in reduced expression. Furthermore, allelic variations (SNPs) affecting ZNF143 binding were found to modify its chromatin interactions. Thus, ZNF143 binding at promoters is required for chromatin looping with distal regulatory elements.