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Histone deacetylase 3 (HDAC3) has low enzymatic activity in vitro unless associated with the nuclear receptor corepressors NCOR1 and SMRT through the deacetylase activation domain (DAD). Mice lacking functional DADs in both NCOR1 and SMRT are born and reach adulthood but lack HDAC3 activity, whereas mice lacking HDAC3 are embryonic lethal, which suggests an essential deacetylase-independent function of HDAC3.
