YY1 Negatively Regulates Mouse Myelin Proteolipid Protein ( PLP1 ) Gene Expression in Oligodendroglial Cells
Open accessAbstract
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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The distal segment of the 2.2 kb human MAG promoter fragment contains binding sites for YY1 and Id4.
“The distal segment of this fragment contained binding sites for both positive and negative transcriptional regulators such as Yin Yang 1 (YY1) and Inhibitor of DNA Binding 4 (Id4; Marin-Husstege et al., 2006; He et al., 2007; Zolova and Wight, 2011).”
From Recombinant Human Myelin-Associated Glycoprotein Promoter Drives Selective AAV-Mediated Transgene Expression in Oligodendrocytes (2016) · cites this paper as Zolova and Wight, 2011
The Results section identifies a YY1-binding motif in the mouse Plp1 promoter, not in a human MAG promoter fragment. Searches for MAG, Id4, and a 2.2 kb promoter fragment found no passage addressing the claimed binding sites; the paper’s findings about Plp1 do not establish them for MAG. (LLM, conf=0.78)
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- Authors
- Zolova, O. E., & Wight, P. A.
- Affiliations
- Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
- University of Arkansas for Medical Sciences (US)
- Corresponding author
- Wight, Patricia A
- Venue
- ASN Neuro
- Publisher
- Informa UK Limited
- Published
- 2011-08
- Volume
- 3
- Issue
- 4
- ISSN
- 1759-0914 (ISSN-L)
- PMC
- PMC3207217
- OpenAlex
- W2100010811
- Cited by
- 15
- References
- 42
- Citations by year
- 2026: 3 · 2024: 1 · 2022: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 4 · 2012: 1
- FWCI
- 0.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- ASN NEURO (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Neurological Disorders and Stroke (P30NS047546, R01NS037821, R01 NS37821)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- YY1, proteolipid protein, oligodendrocytes, transcriptional repression, myelination, zinc finger transcription factor
- MeSH terms
- Animals, Cell Line, Transformed, Introns, Oligodendroglia, Promoter Regions, Genetic, Protein Binding, Transfection, Down-Regulation, Myelin Proteolipid Protein, Electrophoretic Mobility Shift Assay, YY1 Transcription Factor, Mice
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