biostudies-literatureWu YNational Center for Advancing Translational SciencesNCATS NIH HHSHuntsman Cancer Institute, University of UtahNational Institutes of Health110859https://www.ebi.ac.uk/biostudies/studies/S-EPMC12664036biostudies-literatureUnknown301(12)Oct4 is a master regulator of pluripotency. Potential Oct4 interactors have been cataloged but the manner and significance of these interactions are incompletely defined. Oct4 is capable of binding to DNA in multiple configurations, however the relationship between these configurations and cofactor recruitment (and hence transcription output) are unknown. Here, we show that Oct4 interacts with common and unique proteins when bound to DNA in different configurations. A unique protein is Jade1, a component of HBO histone acetyltransferase complexes. Jade1 preferentially associates with Oct4 when bound to more palindromic Octamer-Related Element (MORE) DNA sequences that bind Oct4 dimers. Surprisingly, we find that the Oct4 N-terminal activation domain, rather than facilitating Jade1 binding,The Journal of biological chemistryJade1 and the HBO1 histone acetyltransferase complex are spatial-selective cofactors of the pluripotency transcription factor Oct4.PMC12664036R03 TR0045681R03TR004568Shen ZTantin DChandrasekharan MBHanda HManna AKLi LWu YfalseJade1 and the HBO1 histone acetyltransferase complex are spatial-selective cofactors of the pluripotency transcription factor Oct4.Oct4 is a master regulator of pluripotency. Potential Oct4 interactors have been cataloged but the manner and significance of these interactions are incompletely defined. Oct4 is capable of binding to DNA in multiple configurations, however the relationship between these configurations and cofactor recruitment (and hence transcription output) are unknown. Here, we show that Oct4 interacts with common and unique proteins when bound to DNA in different configurations. A unique protein is Jade1, a component of HBO histone acetyltransferase complexes. Jade1 preferentially associates with Oct4 when bound to more palindromic Octamer-Related Element (MORE) DNA sequences that bind Oct4 dimers. Surprisingly, we find that the Oct4 N-terminal activation domain, rather than facilitating Jade1 binding,2025-01-01T00:00:00Z2025 Dec2026-07-15T06:55:02.05Z2026-06-30T03:31:25.651ZS-EPMC126640364148990010.1016/j.jbc.2025.110859