DNA recognition by normal and oncogenic thyroid hormone receptors

Unexpected diversity in half-site specificity controlled by non-zinc-finger determinants

Catherine Judelson, Martin L. Privalsky

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The nuclear hormone receptors regulate target gene expression in response to hormones of extracellular origin. The DNA binding specificity of these receptors therefore plays the critical role of defining the precise repertoire of target genes that respond to a given hormone. We report here an analysis of the DNA binding specificity of the thyroid hormone receptor (c- ErbA protein) and that of an oncogenic derivative, the v-ErbA protein. These otherwise closely similar proteins exhibit quite divergent DNA sequence specificities at multiple positions within the DNA binding site. The thyroid hormone receptor (c-ErbA protein) exhibits a particularly broad DNA specificity, whereas the v-ErbA protein is comparatively quite specific. Intriguingly, these differences in DNA recognition largely map to an N- terminal receptor domain not traditionally implicated in DNA binding, and are further influenced by heterodimer formation with retinoid X receptors. We propose that the N terminus of nuclear hormone receptors plays an critical role in DNA recognition by altering the conformation of the receptor domains that make the actual base-specific contacts.

Original languageEnglish (US)
Pages (from-to)10800-10805
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number18
DOIs
StatePublished - 1996

Fingerprint

Thyroid Hormone Receptors
Fingers
Oncogene Proteins v-erbA
DNA
Thyroid Hormone Receptors alpha
Cytoplasmic and Nuclear Receptors
Hormones
Retinoid X Receptors
DNA sequences
Gene expression
Conformations
Genes
Binding Sites
Derivatives
Gene Expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

DNA recognition by normal and oncogenic thyroid hormone receptors : Unexpected diversity in half-site specificity controlled by non-zinc-finger determinants. / Judelson, Catherine; Privalsky, Martin L.

In: Journal of Biological Chemistry, Vol. 271, No. 18, 1996, p. 10800-10805.

Research output: Contribution to journalArticle

@article{2751f43b1b474653b8c9e9d7db62c250,
title = "DNA recognition by normal and oncogenic thyroid hormone receptors: Unexpected diversity in half-site specificity controlled by non-zinc-finger determinants",
abstract = "The nuclear hormone receptors regulate target gene expression in response to hormones of extracellular origin. The DNA binding specificity of these receptors therefore plays the critical role of defining the precise repertoire of target genes that respond to a given hormone. We report here an analysis of the DNA binding specificity of the thyroid hormone receptor (c- ErbA protein) and that of an oncogenic derivative, the v-ErbA protein. These otherwise closely similar proteins exhibit quite divergent DNA sequence specificities at multiple positions within the DNA binding site. The thyroid hormone receptor (c-ErbA protein) exhibits a particularly broad DNA specificity, whereas the v-ErbA protein is comparatively quite specific. Intriguingly, these differences in DNA recognition largely map to an N- terminal receptor domain not traditionally implicated in DNA binding, and are further influenced by heterodimer formation with retinoid X receptors. We propose that the N terminus of nuclear hormone receptors plays an critical role in DNA recognition by altering the conformation of the receptor domains that make the actual base-specific contacts.",
author = "Catherine Judelson and Privalsky, {Martin L.}",
year = "1996",
doi = "10.1074/jbc.271.18.10800",
language = "English (US)",
volume = "271",
pages = "10800--10805",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "18",

}

TY - JOUR

T1 - DNA recognition by normal and oncogenic thyroid hormone receptors

T2 - Unexpected diversity in half-site specificity controlled by non-zinc-finger determinants

AU - Judelson, Catherine

AU - Privalsky, Martin L.

PY - 1996

Y1 - 1996

N2 - The nuclear hormone receptors regulate target gene expression in response to hormones of extracellular origin. The DNA binding specificity of these receptors therefore plays the critical role of defining the precise repertoire of target genes that respond to a given hormone. We report here an analysis of the DNA binding specificity of the thyroid hormone receptor (c- ErbA protein) and that of an oncogenic derivative, the v-ErbA protein. These otherwise closely similar proteins exhibit quite divergent DNA sequence specificities at multiple positions within the DNA binding site. The thyroid hormone receptor (c-ErbA protein) exhibits a particularly broad DNA specificity, whereas the v-ErbA protein is comparatively quite specific. Intriguingly, these differences in DNA recognition largely map to an N- terminal receptor domain not traditionally implicated in DNA binding, and are further influenced by heterodimer formation with retinoid X receptors. We propose that the N terminus of nuclear hormone receptors plays an critical role in DNA recognition by altering the conformation of the receptor domains that make the actual base-specific contacts.

AB - The nuclear hormone receptors regulate target gene expression in response to hormones of extracellular origin. The DNA binding specificity of these receptors therefore plays the critical role of defining the precise repertoire of target genes that respond to a given hormone. We report here an analysis of the DNA binding specificity of the thyroid hormone receptor (c- ErbA protein) and that of an oncogenic derivative, the v-ErbA protein. These otherwise closely similar proteins exhibit quite divergent DNA sequence specificities at multiple positions within the DNA binding site. The thyroid hormone receptor (c-ErbA protein) exhibits a particularly broad DNA specificity, whereas the v-ErbA protein is comparatively quite specific. Intriguingly, these differences in DNA recognition largely map to an N- terminal receptor domain not traditionally implicated in DNA binding, and are further influenced by heterodimer formation with retinoid X receptors. We propose that the N terminus of nuclear hormone receptors plays an critical role in DNA recognition by altering the conformation of the receptor domains that make the actual base-specific contacts.

UR - http://www.scopus.com/inward/record.url?scp=17544384086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17544384086&partnerID=8YFLogxK

U2 - 10.1074/jbc.271.18.10800

DO - 10.1074/jbc.271.18.10800

M3 - Article

VL - 271

SP - 10800

EP - 10805

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 18

ER -