ArticleNucleic acids research2011
Regulatory modules function in a non-autonomous manner to control transcription of the mbp gene.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Screening and In Vivo Validation of Key Genes Involved in Myelin Damage in Alzheimer's Disease.Molecular neurobiology · 2025Article
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- 5' Transgenes drive leaky expression of 3' transgenes in Cre-inducible bi-cistronic vectors.Molecular therapy. Methods & clinical development · 2024Article
- A dual role for DNA binding by Runt in activation and repression ofMolecular biology of the cell · 2021Article
- Oligodendrocyte HCN2 Channels Regulate Myelin Sheath Length.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Transcriptional regulators of the Golli/myelin basic protein locus integrate additive and stealth activities.PLoS genetics · 2020Article
- Review
- Targeted insertion of two Mthfr promoters in mice reveals temporal- and tissue-specific regulation.Mammalian genome : official journal of the International Mammalian Genome Society · 2011Article
- Towards resolving the transcription factor network controlling myelin gene expression.Nucleic acids research · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple regulatory modules contribute to the complex expression programs realized by many loci. Although long thought of as isolated components, recent studies demonstrate that such regulatory sequences can physically associate with promoters and with each other and may localize to specific sub-nuclear transcription factories. These associations provide a substrate for putative interactions and have led to the suggested existence of a transcriptional interactome. Here, using a controlled strategy of transgenesis, we analyzed the functional consequences of regulatory sequence interaction within the myelin basic protein (mbp) locus. Interactions were revealed through comparisons of the qualitative and quantitative expression programs conferred by an allelic series of 11 different enhancer/inter-enhancer combinations ligated to a common promoter/reporter gene. In a developmentally contextual manner, the regulatory output of all modules changed markedly in the presence of other sequences. Predicted by transgene expression programs, deletion of one such module from the endogenous locus reduced oligodendrocyte expression levels but unexpectedly, also attenuated expression of the overlapping golli transcriptional unit. These observations support a regulatory architecture that extends beyond a combinatorial model to include frequent interactions capable of significantly modulating the functions conferred through regulatory modules in isolation.
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