Multi-complex integrative structure determination of the human HDAC1/2 interactome

Histone deacetylases (HDACs) 1 and 2 are Class I HDACs that are members of several transcriptional regulatory complexes including coREST, MIER, NuRD, and SIN3. The interaction of each HDAC within the complex is undefined. Our studies utilize Affinity Purification and Crosslinking Mass Spectrometry to define HDAC1 and 2 interactions. We determined the structures of NuRD, SIN3A, and coREST by integrative structural modeling. Lastly, we characterize MHAP1, previously known as C16orf87, define it as a novel member of the MIER HDAC complex, and also obtain a structural model for an HDAC1:MIER1: MHAP1 complex.