Mutations on the surface of HDAC1 reveal molecular determinants of specific complex assembly and their requirement for gene regulation.

ABSTRACT: Histone deacetylase 1 and 2 (HDAC1/2) regulate histone acetylation as catalytic and structural components of six unique multiprotein complex families: SIN3, NuRD, CoREST, MIDAC, MIER, and RERE. Co-immunoprecipitation of HDAC1-Flag followed by mass spectrometry revealed that 92% of HDAC1 in mouse embryonic stem cells resides in three complexes, NuRD (49%), CoREST (28%), and SIN3 (15%). We compared the structures of MTA1:HDAC1 and MIDEAS:HDAC1 to identify critical binding residues on the surface of HDAC1. Surprisingly, a single mutation, Y48E, disrupts binding to all complexes except SIN3. Rescue experiments performed with HDAC1-Y48E in HDAC1/2 double-knockout cells showed that retention of SIN3 binding alone is sufficient for cell viability. Gene expression and histone acetylation patterns

SUBMITTER: Alshehri A 

PROVIDER: S-EPMC12448893 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature