Article of Significant Interest Selected from This Issue by the Editors

CRISPR Manipulation of Endogenous Binding Sites Sheds New Light on THAP11/ZNF143/HCFC1 Binding to Chromatin

HCFC1 is a transcriptional coregulator whose recruitment to key cell cycle control gene promoters has been attributed to THAP11 and ZNF143 transcription factors. Using synthetic, chromatin-integrated constructs and CRISPR/Cas9-mediated genome editing techniques, Vinckevicius et al. (p. 4135–4146) demonstrate that the ACTACA submotif is sufficient to direct the recruitment of THAP11 and HCFC1 to genes bound otherwise only by ZNF143, while removal or mutation of the ACTACA sequence decreases recruitment of these factors to target genes with subsequent alterations in gene expression. This work suggests a cooperative binding model in which the DNA sequence and its spacing and orientations are critical determinants of chromatin occupancy of THAP11, ZNF143, and HCFC1.