Transcriptional Activation and Repression, Two Properties of the Lymphoid‐Specific Transcription Factor Oct‐2a

Friedl, Erika M.; Matthias, Patrick

doi:10.1111/j.1432-1033.1995.308_c.x

Cited by 23 publications

(28 citation statements)

References 68 publications

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“…The proline/serine/threonine-rich carboxy-terminal activation domain is critical for B-cell-specific enhancer activation, whereas the amino-terminal glutamine-rich activation domain only marginally contributes to the transactivation function from distal binding sites (1,2,9).…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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 IDs are structurally distinct from the AFs that they regulate (15)(16)(17)(18)(19)(20)(21). In some cases, inhibition is transferable to heterologous AFs, suggesting that the IDs are functionally independent.…”

mentioning

confidence: 99%

“…Such IDs have been identified by deletion mutagenesis that generate proteins with enhanced transcriptional activities. Examples include members of the AP1 family c-Jun (15), c-Fos, and the related protein, FosB (16); ATF-2, a member of the ATF/cAMP regulatory element-binding protein subfamily of basic region leucine zipper (bZIP)-containing transcription factors (17); and the lymphoid-specific transcription factor, Oct-2a (18). An ID has also been found in the proto-oncogene c-Myb, which plays a key role in hematopoesis (19).…”

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confidence: 99%

An N-terminal Inhibitory Function, IF, Suppresses Transcription by the A-isoform but Not the B-isoform of Human Progesterone Receptors

Hovland¹,

Powell

Takimoto

et al. 1998

Journal of Biological Chemistry

131

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The B-isoform of human progesterone receptors (PR) contains three activation functions (AF3, AF1, and AF2), two of which (AF1 and AF2) are shared with the Aisoform. AF3 is in the B-upstream segment (BUS), the far N-terminal 164 amino acids of B-receptors; AF1 is in the 392-amino acid N-terminal region common to both receptors; and AF2 is in the C-terminal hormone binding domain. B-receptors are usually stronger transactivators than A-receptors due to transcriptional synergism between AF3 and one of the two downstream AFs. We now show that the N terminus of PR common to both isoforms contains an inhibitory function (IF) located in a 292-amino acid segment lying upstream of AF1. IF represses the activity of A-receptors but is not inhibitory in the context of B-receptors due to constraints imparted by BUS. As a result, IF inhibits AF1 or AF2 but not AF3, regardless of the position of IF relative to BUS. IF is functionally independent and strongly represses transcription when it is fused upstream of estrogen receptors. These data demonstrate the existence of a novel, transferable inhibitory function, mapping to the PR N terminus, which begins to assign specific roles to this large undefined region.Transcriptional control in response to extracellular signals involves the binding of regulatory proteins to specific enhancer elements of target genes. These proteins contain activation functions (AFs) 1 through which contact is made with the basal transcription machinery either directly or indirectly by means of intermediary coregulatory proteins (1). Progesterone receptors (PR) are members of the nuclear receptor family of ligandinducible transcription factors. These are structurally complex proteins containing multiple functional domains, including a highly conserved central DNA-binding domain (DBD), a moderately well conserved C-terminal hormone-binding domain (HBD), and a poorly conserved, N-terminal region whose function is largely unknown (1).There are two naturally occurring isoforms of PR. The 933-amino acid B-receptors contain an N-terminal 164-amino acid upstream segment (BUS) that is missing in the truncated 769-amino acid A-receptors (2-5). The two PR isoforms have AF1 and AF2 in common (5,6). AF1 maps to a 91-amino acid "proline-rich" segment located just upstream of the DBD and AF2 is located in the HBD (6). BUS, restricted to B-receptors, contains AF3 (5). In general, B-receptors are stronger transactivators than A-receptors (5, 7-9), and only B-receptors can activate transcription in the presence of antiprogestins (9 -11). On the other hand, A-receptors can dominantly inhibit B-receptors (9, 12, 13) as well as other members of the steroid receptor family (14).In addition to AFs, some transcription factors also contain inhibitory domains (IDs) that modulate the activity of the AFs. Such IDs have been identified by deletion mutagenesis that generate proteins with enhanced transcriptional activities. Examples include members of the AP1 family c-Jun (15), c-Fos, and the related protein, FosB (16); ATF-2, a ...

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“…There is strong evidence from in vitro experiments to suggest that the Oct-2 C-terminal transcriptional activation domain has unique properties, including an ability to activate transcription from a distal position (16,(23)(24)(25). This property is not observed for the N-terminal activation domain of Oct-2, or for any domain of the related protein Oct-1.…”

mentioning

confidence: 91%

“…These are abilities to activate transcription from a distal position and to interact with a B cell-specific activity to mediate tissue-specific expression (23,24,44). In the plasmacytoma crossed to T lymphoma hybrids of Sharif et al (25), the Oct-2 C terminus was critical for the preservation of the plasma cell gene expression program in hybrid cells in vitro.…”

Section: The Oct-2 Ctd Is Indispensable For Oct-2 Function In Vivomentioning

confidence: 99%

All Known In Vivo Functions of the Oct-2 Transcription Factor Require the C-Terminal Protein Domain

Corcoran

Köentgen²,

Dietrich

et al. 2004

The Journal of Immunology

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Oct-2, a transcription factor expressed in the B lymphocyte lineage and in the developing CNS, functions through of a number of discrete protein domains. These include a DNA-binding POU homeodomain flanked by two transcriptional activation domains. In vitro studies have shown that the C-terminal activation domain, a serine-, threonine- and proline-rich sequence, possesses unique qualities, including the ability to activate transcription from a distance in a B cell-specific manner. In this study, we describe mice in which the endogenous oct-2 gene has been modified through gene targeting to create a mutated allele, oct-2ΔC, which encodes Oct-2 protein isoforms that lack all sequence C-terminal to the DNA-binding domain. Surprisingly, despite the retention of the DNA-binding domain and the glutamine-rich N-terminal activation domain, the truncated protein(s) encoded by the oct-2ΔC allele are unable to rescue any of the previously described defects exhibited by oct-2 null mice. Homozygous oct-2ΔC/ΔC mice die shortly after birth, and B cell maturation, B-1 cell self renewal, serum Ig levels, and B lymphocyte responses to in vitro stimulation are all reduced or absent, to a degree equivalent to that seen in oct-2 null mice. We conclude that the C-terminal activation domain of Oct-2 is required to mediate the unique and indispensable functions of the Oct-2 transcription factor in vivo.

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Transcriptional Activation and Repression, Two Properties of the Lymphoid‐Specific Transcription Factor Oct‐2a

Cited by 23 publications

References 68 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

An N-terminal Inhibitory Function, IF, Suppresses Transcription by the A-isoform but Not the B-isoform of Human Progesterone Receptors

All Known In Vivo Functions of the Oct-2 Transcription Factor Require the C-Terminal Protein Domain

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