Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase

Mol Cell Endocrinol. 2003 Aug 29;206(1-2):1-12. doi: 10.1016/s0303-7207(03)00254-5.


A direct interaction between the nuclear receptor TR2 and histone deacetylases (HDACs) 3 and 4 is mediated by the DNA binding domain (DBD) of TR2. To test if this interaction is common to members of the nuclear receptor family, the Cys2-Cys2 type zinc finger (ZF) DBDs were subcloned from several nuclear receptors (mRARalpha, mRXRbeta, mTR2, mTR4, RAR, mPPARdelta, and mPPARgamma2). Using GST pull-downs, both HDACs 3 and 4 were found to interact directly with the core DBD from each receptor. The three-dimensional structure of the ZF domains was essential for this interaction as disruption by zinc chelation precluded interaction with HDACs. The results suggest that the ZFs of nuclear receptors provide a general interaction interface for HDACs 3 and 4. Functional significance of this interaction was demonstrated using ChIP assays where a truncated TR2 protein (lacking the LBD) recruited HDACs 3 and 4 to the target DNA causing demonstrable histone deacetylation. GST pull-downs and mammalian two-hybrid interaction tests were then used to define the interaction domains of HDAC3 with TR2. Both the N- and C-terminal portions of HDAC3 showed interaction with the TR2 DBD. Thus, multiple domains of HDAC3 form the interaction surface for the DBD of nuclear receptors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Cloning, Molecular
  • DNA-Binding Proteins / metabolism*
  • Histone Deacetylases / metabolism*
  • Humans
  • Mice
  • Nuclear Receptor Subfamily 2, Group C, Member 1
  • Protein Binding
  • Protein Interaction Mapping
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Thyroid Hormone / metabolism
  • Repressor Proteins / metabolism
  • Zinc Fingers


  • DNA-Binding Proteins
  • NR2C1 protein, human
  • Nr2c1 protein, mouse
  • Nuclear Receptor Subfamily 2, Group C, Member 1
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Thyroid Hormone
  • Repressor Proteins
  • HDAC4 protein, human
  • Histone Deacetylases
  • histone deacetylase 3