Twin of I-POU: A two amino acid difference in the I-POU homeodomain distinguishes an activator from an inhibitor of transcription

Treacy, Maurice N.; Neilson, Lorna; Turner, Eric E.; He, Xi; Rosenfeld, Michael G.

doi:10.1016/0092-8674(92)90186-g

Cited by 108 publications

(71 citation statements)

References 81 publications

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“…Similar interactions occur between HMG-2 and Oct-1 and Oct-6 and between HMG-I/Y and Oct-6 (18,60). In addition, interactions with a POU domain can also result in negative regulation, as has been demonstrated by the inhibition of DNA binding of the Drosophila protein Cf1a upon dimerization with I-POU (50). In each of these examples, the cofactor interacts with the POU domain rather than with the transactivation domains.…”

Section: Discussionmentioning

confidence: 77%

The Carboxy-Terminal Transactivation Domain of Oct-4 Acquires Cell Specificity through the POU Domain

Brehm

Ohbo

Schöler

1997

Molecular and Cellular Biology

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The POU transcription factor Oct-4 is expressed in totipotent and pluripotent cells of the early mouse embryo and the germ cell lineage. Transactivation capacities of regions flanking the DNA binding domain of Oct-4 were analyzed in undifferentiated and differentiated cell lines. The amino-and carboxy-terminal regions (N domain and C domain) fused to the Gal4 DNA binding domain both functioned as transactivation domains in all cell lines tested. However, the C domain failed to activate transcription in some cell lines in the context of the native protein. The underlying regulatory mechanism appears to involve the POU domain of Oct-4 and can discriminate between different POU domains, since constructs in which the C domain was instead fused to the POU domain of Pit-1 were again equally active in all cell lines. These results indicate that the C domain is subject to cell-type-specific regulation mediated by the Oct-4 POU domain. Phosphopeptide analysis revealed that the cell-type-specific difference of C-domain activity correlates with a difference in Oct-4 phosphorylation status. Since Oct-4 is expressed in a variety of distinct cell types during murine embryogenesis, these results suggest an additional regulatory mechanism for determining Oct-4 function in rapidly changing cell types during development.The octamer motif is a regulatory DNA element involved in both ubiquitous and cell-type-specific gene expression and is recognized by a family of eukaryotic transcription factors that share a homologous bipartite DNA binding domain, the POU domain (13,44,52,55). The POU domain consists of two structurally independent subdomains: a 75-amino-acid aminoterminal region specific for this class of transcription factors (POU S ) and a 60-amino-acid carboxy-terminal homeodomain (POU H ). Both subdomains make specific contacts with DNA through a helix-turn-helix structure (17) and are connected by a variable linker that can vary from 15 to 56 amino acids (aa) in length.Regions outside the POU domain are not critical for DNA binding and show little sequence conservation. In many cases,

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Section: Discussionmentioning

confidence: 77%

The Carboxy-Terminal Transactivation Domain of Oct-4 Acquires Cell Specificity through the POU Domain

Brehm

Ohbo

Schöler

1997

Molecular and Cellular Biology

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“…Our results, obtained by using a transcriptional functional assay, suggest a protein competition between Wt and γ (or δ) POU1F1 and a mediator transcription factor or a nuclear protein involved in a structural organization of the chromatin. There are some examples of transcriptional activators and repressors that are encoded by the same gene, namely, the I-POU and its alternative splice form (twin of I-POU), in Drosophila melanogaster, that act as inhibitor and activator of gene transcription (Treacy et al, 1992). Regarding the POU1F1 gene, Voss et al (1993) described an alternative spliced form (Pit-1Δ4) in rat, lacking exon 4, and confirmed that it was not competent in the activation of prolactin promotor.…”

Section: Discussionmentioning

confidence: 93%

Identification and characterization of four splicing variants of ovine POU1F1 gene

Bastos

Ávila

Cravador

et al. 2006

Gene

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Expression of POU1F1 gene, a member of the POU homeodomain family of transcription factors, is necessary for normal differentiation, development and survival of three anterior pituitary cell types (thyrotrophs, somatotrophs and lactotrophs) and for the proper expression of growth hormone (GH ), prolactin (PRL), thyroid-stimulating hormone (TSH ) genes and POU1F1 gene itself. Alternative splicing forms of this gene have been reported in different species, with few functional studies. Apart from the POU1F1-Wild-type with the expected length, in this work we isolated three additional splicing variants: POU1F1-β, with a 78 bp insert in the trans-activation domain; POU1F1-γ that lacks exon 3 and POU1F1-δ that lacks exons 3, 4 and 5. Four different protein isoforms were also detected by Western blot in the sheep pituitary tissue. Functional assays were performed to study the trans-activation of GH and PRL promoters by the splicing variants. Regarding the PRL promoter, the β variant presented only 12% of the Wild-type trans-activation capacity. Variants γ and δ showed no capacity to trans-activate PRL promoter. Both γ and δ variants acted as repressors of Wt, reducing significantly the trans-activation made by Wt alone ( p < 0.05). Concerning the GH promoter, the β variant presented a trans-activation capacity 10% higher than Wt. Wt and β variants strongly interact in the activation of GH promoter doubling the trans-activation potential of Wt. Variants γ and δ showed no capacity to trans-activate the GH promoter and both acted as repressors, reducing significantly ( p < 0.001) the trans-activation performed by Wt. This work presents, for the first time, the characterization of four splicing forms of Ovis aries POU1F1 gene.

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“…Therefore, protein-protein in teractions between different HOM (or Hox) proteins, or between these proteins and other components of the transcriptional machinery, could be critical factors in the regulation of HOM/Hox functional specificity (Hayashi and Scott 1990;McGirmis and Krumlauf 1992). In the case of other homeo domain-containing proteins, protein-protein interactions do play a role in enhancing DNA-binding specificity and/or regulating their func tions (see Manak and Scott 1993), the best characterized examples being the yeast MAT (Smith and Johnson 1992) and the POU (Stem et al 1989;Treacy et al 1992;Verrijzer et al 1992) transcription factors. So far, however, products of the HOM/Hox family genes were not known to establish protein-protein interactions among them selves and/or with other factors, even though such in teractions have been postulated in several cases in order to explain their mechanism of action (Jaynes and OTarrell 1988;Han et al 1989;Jaynes and O'Farrel 1991;Fitzpatrick et al 1992;Ananthan et al 1993;FurukuboTokunaga et al 1993;Schier and Gehring 1993).…”

mentioning

confidence: 99%

Specificity of HOX protein function depends on DNA-protein and protein-protein interactions, both mediated by the homeo domain.

Zappavigna

Sartori²,

Mavilio³

1994

Genes Dev.

124

117

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Twin of I-POU: A two amino acid difference in the I-POU homeodomain distinguishes an activator from an inhibitor of transcription

Cited by 108 publications

References 81 publications

The Carboxy-Terminal Transactivation Domain of Oct-4 Acquires Cell Specificity through the POU Domain

The Carboxy-Terminal Transactivation Domain of Oct-4 Acquires Cell Specificity through the POU Domain

Identification and characterization of four splicing variants of ovine POU1F1 gene

Specificity of HOX protein function depends on DNA-protein and protein-protein interactions, both mediated by the homeo domain.

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