DNA binding specificity and function of retinoid X receptor alpha.

Retinoid X receptors are members of the erbA superfamily of ligand-inducible transcription factors. Similar to several other members of this gene family, retinoid X receptors are known to bind to the hexameric DNA sequence AGGTCA. After binding to a direct repeat of this hexamer with a one-base pair spacer, retinoid X receptor homodimers are able to activate transcription in the presence of the ligand 9-cis-retinoic acid. However, it is not known if AGGTCA represents the highest affinity binding site for retinoid X receptors. A combination of the electrophoretic mobility shift assay and polymerase chain reaction was used to isolate from a pool of random DNA those sequences that bind retinoid X receptors with highest affinity. This approach, combined with mutational analysis and DNA footprinting, led to the identification of the seven-base pair sequence GGGGTCA as the highest affinity retinoid X receptor binding site. A direct repeat of this sequence is substantially more active than a direct repeat of AGGTCA as a retinoid X response element.

• Publication year

  1994

• Venue

  Journal of Biological Chemistry

• Publication date

  1994-12-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/s0021-9258(18)43802-1PMID 7982932
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• DNA sequences that act as high affinity targets for the vitamin D3 receptor in the absence of the retinoid X receptor.

  1994cited by this paper
• Dimerization interfaces formed between the DNA binding domains determine the cooperative binding of RXR/RAR and RXR/TR heterodimers to DR5 and DR4 elements.

  1994cited by this paper
• Nucleotide substitutions differentially affect direct repeat and palindromic thyroid hormone response elements.

  1994cited by this paper
• Two nuclear signalling pathways for vitamin D

  1993cited by this paper
• The orphan receptor Rev-ErbA alpha activates transcription via a novel response element

  1993cited by this paper
• Differential orientations of the DNA-binding domain and carboxy-terminal dimerization interface regulate binding site selection by nuclear receptor heterodimers.

  1993cited by this paper
• Nonbiased identification of DNA sequences that bind thyroid hormone receptor alpha 1 with high affinity.

  1993cited by this paper
• Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling

  1992cited by this paper
• Uracil interference, a rapid and general method for defining protein-DNA interactions involving the 5-methyl group of thymines: the GCN4-DNA complex.

  1992cited by this paper
• 9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRα

  1992cited by this paper
• H‐2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes.

  1992cited by this paper
• Participation of non-zinc finger residues in DNA binding by two nuclear orphan receptors.

  1992cited by this paper
• Retinoid X receptor RXR alpha binds to and trans-activates the hepatitis B virus enhancer.

  1992cited by this paper
• Characterization of three RXR genes that mediate the action of 9-cis retinoic acid.

  1992cited by this paper
• RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors.

  1992cited by this paper
• 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor.

  1992cited by this paper
• Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently.

  1992cited by this paper
• Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors

  1992cited by this paper
• A retinoic acid-responsive element in the apolipoprotein AI gene distinguishes between two different retinoic acid response pathways

  1991cited by this paper
• A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR.

  1991cited by this paper
• Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors.

  1991cited by this paper
• RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements.

  1991cited by this paper
• The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors.

  1991cited by this paper
• Identification of the DNA binding site for NGFI-B by genetic selection in yeast.

  1991cited by this paper
• Nuclear receptor that identifies a novel retinoic acid response pathway

  1990cited by this paper
• Sequence-specific DNA binding by the c-Myc protein.

  1990cited by this paper
• Determinants of target gene specificity for steroid/thyroid hormone receptors.

  1989cited by this paper
• H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element.

  1989cited by this paper
• A versatile in vivo and in vitro eukaryotic expression vector for protein engineering

  1988cited by this paper
• Isolation of a cDNA clone encoding a biologically active thyroid hormone receptor.

  1988cited by this paper
• CAT vectors for analysis of eukaryotic promoters and enhancers.

  1986cited by this paper

• Towards a unified molecular mechanism for liganddependent activation of NR4A-RXR heterodimers

  2025cites this paper
• Molecular basis of ligand-dependent Nurr1-RXRα activation

  2022cites this paper
• How could clock gene variants contribute to the causes of autism

  2011cites this paper
• Variable RXR requirements for thyroid hormone responsiveness of endogenous genes.

  2007cites this paper
• Engineering a better receptor: Characterization of retinoid X receptor alpha and functional variants

  2007cites this paper
• Sequences required for the transition from monomeric to homodimeric forms of thyroid hormone receptor alpha and v-erbA.

  2003cites this paper
• Sequences required for the transition from monomeric to homodimeric forms of thyroid hormone receptor α and v-erbA

  2003cites this paper
• Retinoid X receptors and retinoid response in neuroblastoma cells

  2002cites this paper
• Androgen receptor interactions with Oct-1 and Brn-1 are physically and functionally distinct.

  2002cites this paper
• Thyroid Hormone Response Element Sequence and the Recruitment of Retinoid X Receptors for Thyroid Hormone Responsiveness*

  2001cites this paper
• Identification of the DNA Binding Specificity and Potential Target Genes for the Farnesoid X-activated Receptor*

  2000cites this paper
• Dimerization Interfaces of v-ErbA Homodimers and Heterodimers with Retinoid X Receptor α*

  2000cites this paper
• Characterization of the DNA-binding and dominant negative activity of v-erbA homodimers.

  1998cites this paper
• Identification of a Retinoid/Chicken Ovalbumin Upstream Promoter Transcription Factor Response Element in the Human Retinoid X Receptor γ2 Gene Promoter*

  1997cites this paper
• Uremic toxins and vitamin D metabolism.

  1997cites this paper
• Effect of glucose on the function of the calcitriol receptor and vitamin D metabolism.

  1997cites this paper
• Effect of glyoxylate on the function of the calcitriol receptor and vitamin D metabolism.

  1997cites this paper
• Identification of an extended half‐site motif required for the function of peroxisome proliferator‐activated receptor α

  1997cites this paper
• 5 – Molecular Aspects of Ecdysteroid Hormone Action

  1996cites this paper
• Sequence requirements for high affinity retinoid X receptor-alpha homodimer binding.

  1996cites this paper
• Thyroid hormone receptor variant alpha2. Role of the ninth heptad in dna binding, heterodimerization with retinoid X receptors, and dominant negative activity.

  1996cites this paper
• Sequence requirements for high affinity retinoid X receptor-α homodimer binding

  1996cites this paper
• Inhibition of calcitriol receptor binding to vitamin D response elements by uremic toxins.

  1995cites this paper
• Comparison of the DNA Binding Specificity and Function of v-ErbA and Thyroid Hormone Receptor α1 (*)

  1995cites this paper
• The Interplay of Half-site Sequence and Spacing on the Activity of Direct Repeat Thyroid Hormone Response Elements (*)

  1995cites this paper
• Retinoid X receptor alpha binds with the highest affinity to an imperfect direct repeat response element.

  1995cites this paper