Dual readout of two histone modifications at the same time with synthetic recombinant proteins reveals H3K36me3-H3K9me3 bivalency at weakly transcribed genes. Dual readout of two histone modifications at the same time with synthetic recombinant proteins reveals H3K36me3-H3K9me3 bivalency at weakly transcribed genes

In this proof-of-principle approach we have successfully applied a recombinant heterotypic histone modification interacting domain (HiMID) against H3K9me3 and H3K36me2/3 by using AND logic. We discovered that this new bivalent state is associated with the bodies of weakly transcribed genes and enhancers. Further, we also uncovered that this dual state is enriched in zinc finger coding genes and most likely connected to the zinc finger-Trim28-SetDB1 pathway.