Potentiation of myelin proteolipid protein (<i>Plp</i>) gene expression is mediated through AP‐1‐like binding sites

Dobretsova, Anna; Kokorina, Natalia A.; Wight, P.A.L.

doi:10.1111/j.1471-4159.2004.02683.x

Cited by 10 publications

(35 citation statements)

References 45 publications

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“…The transcription start point is indicated by a bent arrow near the end of exon 1. A positive regulatory element called the ASE (green star) is located within the first intron at positions 1093–1177 (Dobretsova et al, 2004), based upon numbering the entire intron from positions 1–8140 (Wight and Dobretsova, 1997). Plp1-lacZ constructs pertinent to this study are depicted directly below the gene.…”

Section: Resultsmentioning

confidence: 99%

“…For instance, PLPΔ809–5807 is missing Plp1 intron 1 DNA from positions 809–5807 based upon numbering the entire intron from positions 1–8140 (Wight and Dobretsova, 1997). Plasmid PLPΔ809–5807 +F(-AP4) (Dobretsova et al, 2004) contains the ASE sequence ( Plp1 intron 1 positions 1093–1177) inserted into the PstI site at the deletion–junction site of PLPΔ809–5807 in the native (forward; F) orientation, and is referred to here as PLPΔ809–5807+ASE-F for purposes of clarity.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, we designated the positive regulatory element ASE ( a nti- s ilencer/ e nhancer). The ASE has been minimally mapped to mouse Plp1 intron 1 positions 1093–1177 (Dobretsova et al, 2004) and contains an exact match to a high affinity YY1 target site (consensus = VDCCATNWY; Yant et al, 1995) spanning intron 1 positions 1137–1145. The intron also contains nine other potential YY1 binding sites with exact matches to the CCAT core consensus sequence.…”

Section: Introductionmentioning

confidence: 99%

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YY1 Negatively Regulates Mouse Myelin Proteolipid Protein (PLP1) Gene Expression in Oligodendroglial Cells

Zolova

Wight

2011

ASN Neuro

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YY1 (Yin and Yang 1) is a multifunctional, ubiquitously expressed, zinc finger protein that can act as a transcriptional activator, repressor, or initiator element binding protein. Previous studies have shown that YY1 modulates the activity of reporter genes driven by the myelin PLP (proteolipid protein) (PLP1/Plp1) promoter. However, it is known that Plp1 intron 1 DNA contains regulatory elements that are required for the dramatic increase in gene activity, coincident with the active myelination period of CNS (central nervous system) development. The intron in mouse contains multiple prospective YY1 target sites including one within a positive regulatory module called the ASE (anti-silencer/enhancer) element. Results presented here demonstrate that YY1 has a negative effect on the activity of a Plp1-lacZ fusion gene [PLP(+)Z] in an immature oligodendroglial cell line (Oli-neu) that is mediated through sequences present in Plp1 intron 1 DNA. Yet YY1 does not bind to its alleged site in the ASE (even though the protein is capable of recognizing a target site in the promoter), indicating that the down-regulation of PLP(+)Z activity by YY1 in Oli-neu cells does not occur through a direct interaction of YY1 with the ASE sequence. Previous studies with Yy1 conditional knockout mice have demonstrated that YY1 is essential for the differentiation of oligodendrocyte progenitors. Nevertheless, the current study suggests that YY1 functions as a repressor (not an activator) of Plp1 gene expression in immature oligodendrocytes. Perhaps YY1 functions to keep the levels of PLP in check in immature cells before vast quantities of the protein are needed in mature myelinating oligodendrocytes.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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YY1 Negatively Regulates Mouse Myelin Proteolipid Protein (PLP1) Gene Expression in Oligodendroglial Cells

Zolova

Wight

2011

ASN Neuro

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“…Since clinical PLP1 mutation testing only examines the exons, and the proximal portions of the 5′ and 3′ regions and of the introns, it is possible that some of the remaining patients have mutations in these non-coding regions that lie outside the currently analyzed regions. There is at least one well-characterized regulatory region deep within the large first intron of the murine Plp1 gene [153]. Mutations in an equivalent region of the human gene would be expected to cause a PMD syndrome.…”

Section: Additional Genotype-phenotype Correlationsmentioning

confidence: 99%

Pelizaeus-Merzbacher disease: Genetic and cellular pathogenesis

Garbern

2006

Cell. Mol. Life Sci.

165

147

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Pelizaeus-Merzbacher disease (PMD) and the allelic spastic paraplegia type 2 (SPG2) arise from mutations in the X-linked gene encoding myelin proteolipid protein (PLP). Analysis of mutations affecting PLP, the major protein in central nervous system myelin, has revealed previously unsuspected roles for myelinating glia in maintaining the integrity of the nervous system. The disease spectrum for PMD and SPG2 is extraordinarily broad and can be best understood by accounting not only for the wide range of mutations that can occur but also for the effects of PLP1 mutations on both cell autonomous and non-cell autonomous processes in myelinating cells. Appreciating the wide range of genetic and cellular effects of PLP1 mutations is important for patient and family counseling, understanding disease pathogenesis, and, ultimately, for developing future disease-specific therapies.

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“…ASE contains several AP-1 like binding sites (Dobretsova et al, 2004), differentially binds nuclear proteins from diverse cell types, and functions in reporter constructs with both the plp/DM20 proximal promoter, and, in a position-dependent manner, with a thymidine kinase (TK ) promoter when transfected into a plp/DM20-expressing oligodendrocyte cell line (Meng et al, 2005). In contrast, neither the ASE2538 nor ASE300 constructs expressed in oligodendrocytes, Schwann cells, satellite cells, or OECs in transgenic mice.…”

Section: Discussionmentioning

confidence: 99%

Separate Proteolipid Protein/DM20 Enhancers Serve Different Lineages and Stages of Development

Tuason¹,

Rastikerdar²,

Kuhlmann³

et al. 2008

Journal of Neuroscience

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The gene encoding DM20 emerged in cartilaginous fish, descending from a bilaterian ancestor of the M6 proteolipid gene family. Its proteolipid protein (PLP) isoform appeared in amphibians, contains an additional 35 amino acids, and, in the mammalian CNS, is the dominant myelin protein in which it confers an essential neuroprotective function. During development, the DM20 isoform is prominent in a number of tissues, and plp/DM20 transcripts are detected in multiple progenitor populations, including those that continue to express plp/DM20 as they differentiate into myelinating oligodendrocytes. The locus also encodes isoforms with extended leader sequences that accumulate in the cell bodies of several types of neurons. Here, to locate and characterize regulatory sequences controlling the complex plp/DM20 transcription program, putative regulatory sequences, suggested by interspecies conservation, were ligated individually to a minimally promoted eGFPlacZ reporter gene. These constructs were inserted in single copy at a common site adjacent to the hypoxanthine-guanine phosphoribosyltransferase locus in embryonic stem cells and their in vivo expression programs were compared in transgenic mice. Most expressed developmental and cell-specific subprograms accommodated within the known expression phenotype of the endogenous plp/DM20 locus, thus defining multiple components of the combinatorial mechanism controlling its normal temporal and cell-specific program. Along with previously characterized nervous system enhancers, those described here should help expose the content and configuration of elements that are operational in multiple glial and neuronal lineages. The transgenic lines derived here also provide effective markers for multiple stages of glial and neuronal lineage progression.

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Potentiation of myelin proteolipid protein (Plp) gene expression is mediated through AP‐1‐like binding sites

Cited by 10 publications

References 45 publications

YY1 Negatively Regulates Mouse Myelin Proteolipid Protein (PLP1) Gene Expression in Oligodendroglial Cells

YY1 Negatively Regulates Mouse Myelin Proteolipid Protein (PLP1) Gene Expression in Oligodendroglial Cells

Pelizaeus-Merzbacher disease: Genetic and cellular pathogenesis

Separate Proteolipid Protein/DM20 Enhancers Serve Different Lineages and Stages of Development

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