SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers

Matthew R. Hass, Hien haw Liow, Xiaoting Chen, Ankur Sharma, Yukiko U. Inoue, Takayoshi Inoue, Ashley Reeb, Andrew Martens, Mary Fulbright, Saravanan Raju, Michael Stevens, Scott Boyle, Joo Seop Park, Matthew T. Weirauch, Michael R. Brent, Raphael Kopan

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


We developed Split DamID (SpDamID), a protein complementation version of DamID, to mark genomic DNA bound in vivo by interacting or juxtapositioned transcription factors. Inactive halves of DAM (DNA adenine methyltransferase) were fused to protein pairs to be queried. Either direct interaction between proteins or proximity enabled DAM reconstitution and methylation of adenine in GATC. Inducible SpDamID was used to analyze Notch-mediated transcriptional activation. We demonstrate that Notch complexes label RBP sites broadly across the genome and show that a subset of these complexes that recruit MAML and p300 undergo changes in chromatin accessibility in response to Notch signaling. SpDamID differentiates between monomeric and dimeric binding, thereby allowing for identification of half-site motifs used by Notch dimers. Motif enrichment of Notch enhancers coupled with SpDamID reveals co-targeting of regulatory sequences by Notch and Runx1. SpDamID represents a sensitive and powerful tool that enables dynamic analysis of combinatorial protein-DNA transactions at a genome-wide level.

Original languageEnglish
Pages (from-to)685-697
Number of pages13
JournalMolecular cell
Issue number4
StatePublished - Aug 20 2015


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