The POU Factor Oct-6 and Schwann Cell Differentiation

Jaegle, Martine; Mandemakers, Wim; Broos, Ludo A. M.; Zwart, Ronald; Karis, Alar; Visser, Pim; Grosveld, Frank; Meijer, Dies

doi:10.1126/science.273.5274.507

Cited by 274 publications

(279 citation statements)

References 17 publications

Supporting

Mentioning

258

Contrasting

Unclassified

Order By: Relevance

“…Such factors, particularly those of the POU-III family, which include Brn2, Brn4, and SCIP, play roles in the differentiation of neuronal and glial cell populations. For example, gene knockout of Brn2 (38) disrupts the differentiation of neurons in the hypothalamus and pituitary gland, and knockout of SCIP (39,40) prevents differentiation of Schwann cells. In our cotransfection experiments that examined the regulation of the TN promoter by Brn2, Brn4, and SCIP, only Brn2 activated the TN promoter in an octamer-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Multiple promoter elements differentially regulate the expression of the mouse tenascin gene

Copertino

Edelman

Jones

1997

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Tenascin (TN) is an extracellular matrix glycoprotein that is expressed in a characteristic spatiotemporal pattern during development and is up-regulated in the adult during tumorigenesis, wound healing, and nerve regeneration. In previous studies, we identified a promoter within the proximal 250 bp upstream of the mouse TN gene that contains several putative regulatory elements that are conserved among vertebrate TN genes. We have identified four different DNA elements within this promoter and show that they contribute in different ways to TN gene expression in NIH 3T3 fibroblasts, C6 glioma cells, and N2A neuroblastoma cells. These elements comprise a binding site for Krox proteins, one for nuclear factor 1, an octamer motif that binds POU-homeodomain proteins, and a novel TN control element. The nuclear factor 1 and TN control element had positive effects on TN promoter activity and formed similar DNAprotein complexes with nuclear extracts from all three cell lines. The Krox element had a negative effect on TN promoter activity in N2A cells, a positive effect in C6 cells, and no effect in NIH 3T3 cells. Two DNA binding complexes, one correlated with the negative and the other with the positive activities of the Krox element, were found to contain the protein Krox24. In cotransfection experiments, the octamer motif was required for induction of TN promoter activity by the POUhomeodomain protein Brn2 in N2A cells but was inactive in C6 cells. Consistent with these findings, N2A cells transfected with Brn2 formed octamer-binding complexes containing N-Oct3, the transcriptionally active form of Brn2, whereas complexes formed in C6 cells contained only N-Oct5A and N-Oct5B. Our results provide a striking example of the diversity of regulatory mechanisms that can be called forth by combining different promoter motifs with transcriptional activators or repressors.

show abstract

Section: Discussionmentioning

confidence: 99%

Multiple promoter elements differentially regulate the expression of the mouse tenascin gene

Copertino

Edelman

Jones

1997

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Other pro-myelin transcription factors include Oct-6 and to a lesser extent Brn-2. These are important in immature Schwann cells for the correct timing of myelination, and in addition, Sox-10, which besides its importance for the generation of Schwann cell precursors (SCPs), is required for Oct-6 expression in immature Schwann cells and the activation of myelin genes (Bermingham et al, 1996;Britsch et al, 2001;Jaegle et al, 1996;Schreiner et al, 2007) [reviewed in (Jessen and Mirsky, 2005;Topilko and Meijer, 2001)]. In vitro experiments indicate that the myelination machinery also includes the transcription factor NFjB and that this factor may act as a mediator of cyclic AMP (cAMP) signaling (below) (Nickols et al, 2003;Yoon et al, 2008).…”

Section: Positive Regulators Of Myelinationmentioning

confidence: 99%

Negative regulation of myelination: Relevance for development, injury, and demyelinating disease

Jessen

Mirsky

2008

Glia

446

409

View full text Add to dashboard Cite

Dedifferentiation of myelinating Schwann cells is a key feature of nerve injury and demyelinating neuropathies. We review recent evidence that this dedifferentiation depends on activation of specific intracellular signaling molecules that drive the dedifferentiation program. In particular, we discuss the idea that Schwann cells contain negative transcriptional regulators of myelination that functionally complement positive regulators such as Krox-20, and that myelination is therefore determined by a balance between two opposing transcriptional programs. Negative transcriptional regulators should be expressed prior to myelination, downregulated as myelination starts but reactivated as Schwann cells dedifferentiate following injury. The clearest evidence for a factor that works in this way relates to c-Jun, while other factors may include Notch, Sox-2, Pax-3, Id2, Krox-24, and Egr-3. The role of cell-cell signals such as neuregulin-1 and cytoplasmic signaling pathways such as the extracellular-related kinase (ERK)1/2 pathway in promoting dedifferentiation of myelinating cells is also discussed. We also review evidence that neurotrophin 3 (NT3), purinergic signaling, and nitric oxide synthase are involved in suppressing myelination. The realization that myelination is subject to negative as well as positive controls contributes significantly to the understanding of Schwann cell plasticity. Negative regulators are likely to have a major role during injury, because they promote the transformation of damaged nerves to an environment that fosters neuronal survival and axonal regrowth. In neuropathies, however, activation of these pathways is likely to be harmful because they may be key contributors to demyelination, a situation which would open new routes for clinical intervention. V V C 2008 Wiley-Liss, Inc.

show abstract

“…Comparison of the known mechanisms of development and regulation of myelin-specific gene expression in Schwann cells and oligodendrocytes, however, demonstrate a number of significant differences. First, the transcription factors known to be necessary for normal Schwann cell maturation and PNS myelination, SCI P (Bermingham et al, 1996;Jaegle et al, 1996) and Krox-20 (Topilko et al, 1994), are not required for normal oligodendrocyte maturation or myelination. In addition, the developmental profile of expression of these proteins is different in the two cell types.…”

Section: Transcription Factors and The Regulation Of Schwann Cell Devmentioning

confidence: 99%

Evidence That the Homeodomain Protein Gtx Is Involved in the Regulation of Oligodendrocyte Myelination

et al. 1997

View full text Add to dashboard Cite

We have investigated the patterns of postnatal brain expression and DNA binding of Gtx, a homeodomain transcription factor. Gtx mRNA accumulates in parallel with the RNAs encoding the major structural proteins of myelin, myelin basic protein (MBP), and proteolipid protein (PLP) during postnatal brain development; Gtx mRNA decreases in parallel with MBP and PLP mRNAs in the brains of myelin-deficient rats, which have a point mutation in the PLP gene. Gtx mRNA is expressed in differentiated, postmitotic oligodendrocytes but is not found in oligodendrocyte precursors or astrocytes. These data thus demonstrate that Gtx is expressed uniquely in differentiated oligodendrocytes in postnatal rodent brain and that its expression is regulated in parallel with the major myelin protein mRNAs, encoding MBP and PLP, under a variety of physiologically relevant circumstances.Using a Gtx fusion protein produced in bacteria, we have confirmed that Gtx is a sequence-specific DNA-binding protein, which binds DNA sequences containing a core AT-rich homeodomain binding site. Immunoprecipitation of labeled DNA fragments encoding either the MBP or PLP promoter regions with this fusion protein has identified several Gtx-binding fragments, and we have confirmed these data using an electrophoretic mobility shift assay. In this way we have identified four Gtx binding sites within the first 750 bp of the MBP promoter and four Gtx binding sites within the first 1.3 kb of the PLP promoter. In addition, inspection of the PLP promoter sequence demonstrates the presence of six additional Gtx binding sites. These data, taken together, strongly suggest that Gtx is important for the function of differentiated oligodendrocytes and may be involved in the regulation of myelin-specific gene expression.

show abstract

The POU Factor Oct-6 and Schwann Cell Differentiation

Cited by 274 publications

References 17 publications

Multiple promoter elements differentially regulate the expression of the mouse tenascin gene

Multiple promoter elements differentially regulate the expression of the mouse tenascin gene

Negative regulation of myelination: Relevance for development, injury, and demyelinating disease

Evidence That the Homeodomain Protein Gtx Is Involved in the Regulation of Oligodendrocyte Myelination

Contact Info

Product

Resources

About