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

@article{Franco2003InteractionON,
  title={Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase},
  author={Peter J. Franco and Guangjin Li and Li-na Wei},
  journal={Molecular and Cellular Endocrinology},
  year={2003},
  volume={206},
  pages={1-12}
}
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… Expand
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References

SHOWING 1-10 OF 48 REFERENCES
The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases.
TLDR
It is suggested that repression mediated by unliganded TR2 is mediated, in part, by a direct interaction of this receptor with histone deacetylase proteins. Expand
The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain
TLDR
It is reported here that a protein of relative molecular mass 19,000 encompassing the DNA-binding domain of the glucocorticoid receptor that has been overexpressed in Escherichia coli and purified to homogeneity reversibly ligates two Zn(II) or Cd( II) ions. Expand
The C-terminal Extension (CTE) of the Nuclear Hormone Receptor DNA Binding Domain Determines Interactions and Functional Response to the HMGB-1/-2 Co-regulatory Proteins*
TLDR
It is shown that the DNA binding domain (DBD) is sufficient to account for the selective influence of HMGB-1/-2 on the steroid class of receptors, and that this selectivity is dependent on the C-terminal extension (CTE), amino acid sequences adjacent to the zinc finger core DBD. Expand
Mechanisms of the Mouse Orphan Nuclear Receptor TR2-11-mediated Gene Suppression*
TLDR
Mutation at two consecutive glutamate residues located within the hinge between the last two helices of the ligand-binding domain drastically reduces its DNA-binding affinity and abrogates the suppression activity without compromising its ability to dimerize, indicating that receptor dimerization property can be functionally uncoupled from its suppressive activity. Expand
DNA binding domains in diverse nuclear receptors function as nuclear export signals
TLDR
It is proposed that NLS-mediated import and DBD-mediated export define a shuttling cycle that integrates the compartmentalization and activity of nuclear receptors. Expand
Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway.
TLDR
This work shows that N-CoR and SMRT each associate with HDAC4 in a complex that does not contain mSin3A or HDAC1, the first example of a single corepressor utilizing distinct domains to engage multiple HDAC complexes. Expand
Direct Acetylation of the Estrogen Receptor α Hinge Region by p300 Regulates Transactivation and Hormone Sensitivity*
TLDR
It is shown that the estrogen receptor (ERα) is acetylated in vivo, and the conservation of the ERα acetylation motif in a phylogenetic subset of nuclear receptors suggests that direct acetylators may contribute to additional signaling pathways involved in metabolism and development. Expand
A constitutive nuclear localization signal from the second zinc-finger of orphan nuclear receptor TR2.
The orphan nuclear receptor TR2 and its truncated isoform deleted in the ligand binding domain (LBD) were localized exclusively in the nuclei as revealed by two methods of detection. AnExpand
Molecular determinants of nuclear receptor-corepressor interaction.
TLDR
A model in which discrimination of the different lengths of the coactivator and corepressor interaction helices by the nuclear receptor AF2 motif provides the molecular basis for the exchange of coactivators for corepressors is proposed, with ligand-dependent formation of the charge clamp that stabilizes LXXLL binding sterically inhibiting interaction of the extended core Pressor helix. Expand
Metal-dependent folding and stability of nuclear hormone receptor DNA-binding domains.
TLDR
Characterising linked equilibria for the isolated DNA-binding domains (DBD) of the receptors for estrogen and glucocorticoid shows co-operativity is consistent with observations from equilibrium denaturation, which indicate that the folding event is a two-state process. Expand
...
1
2
3
4
5
...