The architecture of chromatin regulates eukaryotic cell states by controlling transcription factor access to sites of gene regulation. Here we describe a dual transposase–peroxidase approach, integrative DNA and protein tagging (iDAPT), which detects both DNA (iDAPT-seq) and protein (iDAPT-MS) associated with accessible regions of chromatin. In addition to direct identification of bound transcription factors, iDAPT enables the inference of their gene regulatory networks, protein interactors and regulation of chromatin accessibility. We applied iDAPT to profile the epigenomic consequences of granulocytic differentiation of acute promyelocytic leukemia, yielding previously undescribed mechanistic insights. Our findings demonstrate the power of iDAPT as a platform for studying the dynamic epigenomic landscapes and their transcription factor components associated with biological phenomena and disease.

染色质的结构通过控制转录因子进入基因调控位点来调节真核细胞状态。在这里，我们描述了一种双转座酶-过氧化物酶方法，即整合 DNA 和蛋白质标记 (iDAPT)，它检测与染色质可及区域相关的 DNA (iDAPT-seq) 和蛋白质 (iDAPT-MS)。除了直接识别结合的转录因子外，iDAPT 还可以推断它们的基因调控网络、蛋白质相互作用因子和染色质可及性的调控。我们应用 iDAPT 来分析急性早幼粒细胞白血病粒细胞分化的表观基因组结果，产生了以前未描述的机制见解。