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Stage-specific expression of myelin basic protein in oligodendrocytes involves Nkx2.2-mediated repression that is relieved by the Sp1 transcription factor.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2005 Apr 22; Vol. 280 (16), pp. 16284-94. Date of Electronic Publication: 2005 Feb 03. - Publication Year :
- 2005
-
Abstract
- The homeodomain-containing protein Nkx2.2 is critical for the development of oligodendrocyte lineage cells, but the target genes of Nkx2.2 regulation have not been identified. In the present study, we found that the myelin basic protein gene is one of the genes that is regulated by Nkx2.2. Expression of Nkx2.2 represses the expression of myelin basic protein in oligodendrocyte progenitors. Two regulatory elements in the myelin basic protein promoter were identified and found to interact with Nkx2.2 in vitro. Despite their sequence divergence, both sites were involved in the Nkx2.2-mediated repression of the myelin basic protein promoter. Binding of Nkx2.2 also blocked and disrupted the binding of the transcriptional activator Puralpha to the myelin basic protein promoter. Additionally Nkx2.2 recruited a histone deacetylase 1-mSin3A complex to the myelin basic protein promoter. We also found that the transcription factor Sp1 was able to compete off the binding of Nkx2.2 to its consensus binding site in vitro and reversed the repressive effect of Nkx2.2 in vivo. Our data revealed a novel role for Nkx2.2 in preventing the precocious expression of myelin basic protein in immature oligodendrocytes. Based on this study and our previous reports, a model for myelin basic protein gene control is proposed.
- Subjects :
- Animals
Binding Sites
Cell Differentiation physiology
Cyclic AMP Response Element-Binding Protein metabolism
DNA-Binding Proteins
Down-Regulation
Histone Deacetylases metabolism
Homeobox Protein Nkx-2.2
Homeodomain Proteins genetics
Myelin Basic Protein genetics
Oligodendroglia cytology
Promoter Regions, Genetic
Protein Binding
Rats
Transcription Factors genetics
Zebrafish Proteins
Gene Expression Regulation physiology
Homeodomain Proteins metabolism
Myelin Basic Protein metabolism
Oligodendroglia metabolism
Sp1 Transcription Factor metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 280
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15695521
- Full Text :
- https://doi.org/10.1074/jbc.M500491200