extradenticle Raises the DNA binding specificity of homeotic selector gene products

Dijk, Marc A. van; Murre, Cornelis

doi:10.1016/0092-8674(94)90526-6

Cited by 255 publications

(188 citation statements)

References 33 publications

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“…By themselves, Ubx binding is weak, and Exd is undetectable in EMSA; however, the DNAbinding affinity of both proteins increases when incubated together (28,29). Our results indicate that Arix and dHAND can act as transcription partners to activate DBH gene expression.…”

Section: Dhand Interacts Independent Of Dna Bindingmentioning

confidence: 67%

The Interaction between dHAND and Arix at the Dopamine β-Hydroxylase Promoter Region Is Independent of Direct dHAND Binding to DNA

Rychlik

Gerbasi

Lewis

2003

Journal of Biological Chemistry

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Dopamine ␤-hydroxylase (DBH) catalyzes the production of norepinephrine, and its expression defines the noradrenergic phenotype. Transcription factors dHAND, a basic helix-loop-helix protein, and Arix/ Phox2a, a homeoprotein, have been demonstrated to play a role in the differentiation and maintenance of catecholaminergic neurons. Three Arix regulatory sites have been identified in the DBH promoter proximal region, but there is no such evidence for dHAND. Cotransfection with a DBH promoter-luciferase reporter construct plus dHAND or dHAND-E12 expression plasmids did not alter luciferase activity, whereas transfection with Arix resulted in a 2.5-fold stimulation of luciferase activity. However, a 5.5-fold increase was observed when Arix and dHAND were combined, and an 8-fold level of expression was observed when Arix was transfected with a dHAND mutant lacking the basic DNAbinding domain. When the homeodomain sites in the DBH promoter proximal region were mutated, all activity was lost, demonstrating dependence upon Arix-DNA interaction for transcriptional activation. In electrophoretic mobility shift assays, the addition of dHAND decreased the amount of Arix needed to elicit a mobility shift with the DBH homeodomain sites, and the dHAND basic mutant potentiated Arix binding in a manner similar to wild-type dHAND. The dHAND-Arix complex was dissociated upon the addition of an unlabeled competitor containing a homeodomain, but not upon the addition of a competitor containing E-boxes. Arix coprecipitated with antisera directed against recombinant dHAND, demonstrating direct protein-protein interactions. These results indicate that the activation of the DBH promoter by Arix is potentiated by dHAND via a mechanism independent of a direct interaction of dHAND with DNA.Cell-specific transcription is accomplished by the precise and transient interactions of numerous and complex molecular factors. Basic helix-loop-helix (bHLH) 1 proteins are transcription factors that play an important role in the development and differentiation of specific cell types such as neurons (1), appendages (2), and myocytes (3, 4). These bHLH proteins have been shown to bind to defined consensus sites, E-boxes (CANNTG), through the basic domain and require dimerization partners (via helices) to activate transcription. These proteins have been divided into several classes based on structure, function, and tissue specificity. Class I bHLH proteins (E12 and E47) are expressed ubiquitously in all tissues and can function as homodimers, but prefer to form heterodimers with other bHLH proteins (5). Class II proteins (dHAND, NeuroD, and MyoD) are expressed in specific tissues and are believed to be functionally active when complexed with a class I protein (5, 6). dHAND/HAND2 (deciduum, heart, autonomic nervous system, and neural crest cell derivatives) is a 30-kDa member of the class II bHLH protein family (7,8) and has been detected in Xenopus, zebrafish, chicks, mice, and humans (9). dHAND is required for cardiac (7), vascular (10), and craniofacial...

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Section: Dhand Interacts Independent Of Dna Bindingmentioning

confidence: 67%

The Interaction between dHAND and Arix at the Dopamine β-Hydroxylase Promoter Region Is Independent of Direct dHAND Binding to DNA

Rychlik

Gerbasi

Lewis

2003

Journal of Biological Chemistry

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“…These regions can determine transcription activator or repressor function as well as dimerization reactions with other proteins and cooperative binding to target sequences (Wilson et al, 1993). In Drosophila the extradenticle encoded divergent homeodomain protein undergoes cooperative interactions with other homeoproteins to alter their target site specificity (Chan et al, 1994;van Dijk and Murre, 1994). The sum of these different effects, coupled with the distinct developmental expression patterns for individual homeobox genes, likely generates the diverse biological activities of homeobox genes.…”

Section: Gsh-imentioning

confidence: 99%

Gsh‐1: A novel murine homeobox gene expressed in the central nervous system

Valerius

Stock

et al. 1995

Developmental Dynamics

103

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We report the characterization of Gsh-1, a novel murine homeobox gene. Northern blot analysis revealed a transcript of approximately 2 kb in sue present at embryonic days 10.5, 11.5, and 12.5 of development. The cDNA sequence encoded a proline rich motif, a polyalanine tract, and a homeodomain with strong homology to those encoded by the clustered Hox genes. The Gsh-1 expression pattern was determined for days E8.5 to E13.5 by whole mount and serial section in situ hybridizations. Gsh-1 transcription was restricted to the central nervous system. Expression is present in the neural tube and hindbrain as two continuous, bilaterally symmetrical stripes within neural epithelial tissue. In the mesencephalon, expression is seen as a band across the most anterior portion. There is also diencephalon expression in the anlagen of the thalamus and the hypothalamus as well as in the optic stalk, optic recess, and the ganglionic eminence. Moreover, through the use of fusion proteins containing the Gsh-I homeodomain, we have determined the consensus DNA binding site of the Gsh-1 homeoprotein to be GCT/cA/,ATTAG/A. 0 1995 Wiley-Liss, Inc.

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“…While the internal 75% of Pbx proteins, which includes the HD, are highly conserved, the N-and C-terminal ends of Pbx proteins are divergent, implying that these regions mediate unique functions. Extradentical (Exd) is a Pbx homolog in D. Melanogaster that binds DNA cooperatively with several homeotic selector proteins (Rauskolb et al, 1993;Rauskolb and Wieschaus, 1994;van Dijk and Murre C, 1994), and together with these HD proteins, induces appropriate transcription of differentiation genes. This observation laid the foundation for the subsequent discovery that Pbx1 exhibits cooperative DNA-binding with the mammalian homologs of the HOM-C proteins, the Hox proteins, as well as with the Engrailed family of HD proteins.…”

Section: Introductionmentioning

confidence: 99%

The highest affinity DNA element bound by Pbx complexes in t(1;19) leukemic cells fails to mediate cooperative DNA-binding or cooperative transactivation by E2a-Pbx1 and Class I Hox proteins – evidence for selective targetting of E2a-Pbx1 to a subset of Pbx-recognition elements

Knoepfler

Kamps

1997

Oncogene

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extradenticle Raises the DNA binding specificity of homeotic selector gene products

Cited by 255 publications

References 33 publications

The Interaction between dHAND and Arix at the Dopamine β-Hydroxylase Promoter Region Is Independent of Direct dHAND Binding to DNA

The Interaction between dHAND and Arix at the Dopamine β-Hydroxylase Promoter Region Is Independent of Direct dHAND Binding to DNA

Gsh‐1: A novel murine homeobox gene expressed in the central nervous system

The highest affinity DNA element bound by Pbx complexes in t(1;19) leukemic cells fails to mediate cooperative DNA-binding or cooperative transactivation by E2a-Pbx1 and Class I Hox proteins – evidence for selective targetting of E2a-Pbx1 to a subset of Pbx-recognition elements

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