Genome-wide DNA-binding program of CREB3L2-ATF4 heterodimers

We report the development of ChIPmera, a method that resolves the DNA-binding program of dimeric transcription factors in vivo. ChIPmera exploits chemically induced proximity to induce the interaction of specific transcription factor pairs. Each monomer is engineered with two unique features: a specific dimerization domain (FRB or FKBP, C-terminally fused), and an N-terminal epitope tag (HA or V5). They can then be brought together in cells using a bivalent ligand that recognizes both the FRB and the FKBP domains with high affinity. Dimer-specific DNA-binding programs are elucidated from parallel HA and V5 ChIP-seq analyses. Here, CREB3L2-CREB3L2 homodimers and ATF4-ATF4 homodimers were examined alongside CREB3L2-ATF4 heterodimers. ChIPmera background signals were established using a chemically induced Renilla luciferase homodimer. CREB3L2 and ATF4 are transcription factors of the bZIP family.