A developmentally regulated DNA-binding protein from mouse brain stimulates myelin basic protein gene expression.

Haas, Susan; Gordon, Johnthan; Khalili, Kamel

doi:10.1128/mcb.13.5.3103

Cited by 60 publications

(58 citation statements)

References 48 publications

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“…This mechanism addresses the initial event whereby a myelin antigen is made available to the immune system. With the recent report of the larger MBP gene (36), interesting studies on transcriptional factors (37) and the possibility that multiple interacting genes may determine susceptibility in MS (38) …”

Section: Discussionmentioning

confidence: 99%

Myelin in multiple sclerosis is developmentally immature.

Moscarello

Wood²,

Ackerley³

et al. 1994

J. Clin. Invest.

303

275

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The etiology of multiple sclerosis (MS) is considered to involve genetic, environmental, infective, and immunological factors which affect the integrity of a normally assembled myelin sheath, either directly or indirectly resulting in demyelination. In a correlative study involving protein chemical, mass spectrometric, and electron microscopic techniques we have determined that myelin obtained from victims of MS is arrested at the level of the first growth spurt (within the first 6 yr of life) and is therefore developmentally immature. The data supporting this conclusion include (a) the pattern of microheterogeneity of myelin basic protein (MBP); (b) the NH2-terminal acylation of the least cationic component of MBP ("C-8"); (c) the phase transition temperature (TJ) of myelin isolated from victims of MS correlated with the increased proportion of the least cationic component of MBP; and (d) immunogold electron microscopy using an antibody specific for "C-8" showed that the distribution of gold particles in a 2-yr-old infant was similar to the distribution found in a victim of MS. We postulate that this developmentally immature myelin is more susceptible to degradation by one or a combination of factors mentioned above, providing the initial antigenic material to the immune system. (J. Clin. Invest 1994.94:146-154.)

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Section: Discussionmentioning

confidence: 99%

Myelin in multiple sclerosis is developmentally immature.

Moscarello

Wood²,

Ackerley³

et al. 1994

J. Clin. Invest.

303

275

View full text Add to dashboard Cite

show abstract

“…Pur␣ is a nearly ubiquitous protein originally purified from mouse brain based on its ability to bind to the DNA fragment containing a GGCGGA sequence derived from the myelin basic protein (MBP) proximal regulatory region (21,22). At that time, human Pur␣ had been identified as a sequencespecific single-stranded DNA-binding protein with a potential role in DNA replication and it had been sequenced (2,3).…”

mentioning

confidence: 99%

Purα Is Essential for Postnatal Brain Development and Developmentally Coupled Cellular Proliferation As Revealed by Genetic Inactivation in the Mouse

Khalili

Valle

Muralidharan

et al. 2003

Molecular and Cellular Biology

170

228

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“…Several laboratories have demonstrated that relatively small regions of DNA sequence upstream of both the PL P and M BP genes are sufficient for developmental and tissue-specific activation of lacZ expression in oligodendrocytes in transgenic animals (Gow et al, 1992;Goujet-Z alc et al, 1993;Wright et al, 1993;Wrabetz et al, 1995), and transcription factors interacting with these regions have been identified (Berndt et al, 1992;K im and Hudson, 1992;Haas et al, 1993;Wrabetz et al, 1993). Only one of these factors, MyT1, a member of the zinc finger family of DNA-binding proteins, has been shown to be expressed in oligodendrocytes (Armstrong et al, 1995).…”

mentioning

confidence: 99%

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

et al. 1997

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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

A developmentally regulated DNA-binding protein from mouse brain stimulates myelin basic protein gene expression.

Cited by 60 publications

References 48 publications

Myelin in multiple sclerosis is developmentally immature.

Myelin in multiple sclerosis is developmentally immature.

Purα Is Essential for Postnatal Brain Development and Developmentally Coupled Cellular Proliferation As Revealed by Genetic Inactivation in the Mouse

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

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