Molecular Cell Y i

uthe formation of a higher-order, more condensed structure, lead-ing to the repression of gene transcription (Grunstein, 1997; Struhl, 1998; Shogren-Knaak et al., 2006). diates assembly of the HDAC1 complex independently of inositol phosphate. By analogy, we found that a similarly extended re-gion of SMRT is able to mediate interaction with HDAC3 in theClass I HDACs have been reported to be associated with at least four major corepressor complexes. HDAC3 is recruited absence of Ins(1,4,5,6)P4. Addition of Ins(1,4,5,6)P4 to both com-plexes results in a dramatic increase in HDAC activity. Together,somes to the active site of the enzyme. Functional assays of both the HDAC1 and HDAC3 complexes reveal that Ins(1,4,5,6)P4 is a bona fide conserved regulator of class I HDAC complexes