ArticleNucleic acids research2017
Potential role of DNA methylation as a facilitator of target search processes for transcription factors through interplay with methyl-CpG-binding proteins.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Zinc binding of a Cys2His2-type zinc finger protein is enhanced by the interaction with DNA.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Article
- DNA methylation levels of RELN promoter region in ultra-high risk, first episode and chronic schizophrenia cohorts of schizophrenia.Schizophrenia (Heidelberg, Germany) · 2022Article
- Genetic or siRNA inhibition of MBD2 attenuates the UUO- and I/R-induced renal fibrosis via downregulation of EGR1.Molecular therapy. Nucleic acids · 2022Article
- Epigenetics in Alzheimer's Disease.Frontiers in aging neuroscience · 2022Review
- Discrete-state stochastic kinetic models for target DNA search by proteins: Theory and experimental applications.Biophysical chemistry · 2021Review
- Review
- Epigenetic basis of Alzheimer disease.World journal of biological chemistry · 2020Review
- Zinc Finger Readers of Methylated DNA.Molecules (Basel, Switzerland) · 2018Review
- NMR-based investigations into target DNA search processes of proteins.Methods (San Diego, Calif.) · 2018Review
- Systematic prediction of DNA shape changes due to CpG methylation explains epigenetic effects on protein-DNA binding.Epigenetics & chromatin · 2018Article
- The Epigenetics of Alzheimer's Disease: Factors and Therapeutic Implications.Frontiers in genetics · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Eukaryotic genomes contain numerous non-functional high-affinity sequences for transcription factors. These sequences potentially serve as natural decoys that sequester transcription factors. We have previously shown that the presence of sequences similar to the target sequence could substantially impede association of the transcription factor Egr-1 with its targets. In this study, using a stopped-flow fluorescence method, we examined the kinetic impact of DNA methylation of decoys on the search process of the Egr-1 zinc-finger protein. We analyzed its association with an unmethylated target site on fluorescence-labeled DNA in the presence of competitor DNA duplexes, including Egr-1 decoys. DNA methylation of decoys alone did not affect target search kinetics. In the presence of the MeCP2 methyl-CpG-binding domain (MBD), however, DNA methylation of decoys substantially (∼10-30-fold) accelerated the target search process of the Egr-1 zinc-finger protein. This acceleration did not occur when the target was also methylated. These results suggest that when decoys are methylated, MBD proteins can block them and thereby allow Egr-1 to avoid sequestration in non-functional locations. This effect may occur in vivo for DNA methylation outside CpG islands (CGIs) and could facilitate localization of some transcription factors within regulatory CGIs, where DNA methylation is rare.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.