ArticleNucleic acids research2019
Structural basis for effects of CpA modifications on C/EBPβ binding of DNA.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Molecular mechanisms of SIRT1 in regulating ageing and related intervention strategies.Molecular biology reports · 2026Review
- DNA bendability regulates transcription factor binding to nucleosomes.Nature structural & molecular biology · 2025Article
- DNA-binding proteins from MBD through ZF to BEN: recognition of cytosine methylation status by one arginine with two conformations.Nucleic acids research · 2024Article
- Structural basis of water-mediated cis Watson-Crick/Hoogsteen base-pair formation in non-CpG methylation.Nucleic acids research · 2024Article
- The mitoepigenome responds to stress, suggesting novel mito-nuclear interactions in vertebrates.BMC genomics · 2023Article
- Structures of CTCF-DNA complexes including all 11 zinc fingers.Nucleic acids research · 2023Article
- Physicochemical models of protein-DNA binding with standard and modified base pairs.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structural basis for cell type specific DNA binding of C/EBPβ: The case of cell cycle inhibitor p15INK4b promoter.Journal of structural biology · 2022Article
- Aberrant DNA hydroxymethylation reshapes transcription factor binding in myeloid neoplasms.Clinical epigenetics · 2022Article
- Structural basis of DNA methylation-dependent site selectivity of the Epstein-Barr virus lytic switch protein ZEBRA/Zta/BZLF1.Nucleic acids research · 2022Article
- Proteins That Read DNA Methylation.Advances in experimental medicine and biology · 2022Article
- Analysis of Il36a induction by C/EBPβ via a half-CRE•C/EBP element in murine macrophages in dependence of its CpG methylation level.Genes and immunity · 2021Article
- Structural insights into glucocorticoid receptor function.Biochemical Society transactions · 2021Review
- Molecular mechanism of methyl-dependent and spatial-specific DNA recognition of c-Jun homodimer.Journal of molecular modeling · 2021Article
- Preferential CEBP binding to T:G mismatches and increased C-to-T human somatic mutations.Nucleic acids research · 2021Article
- Tet2 Inactivation Enhances the Antitumor Activity of Tumor-Infiltrating Lymphocytes.Cancer research · 2021Article
- Sleep deprivation and diet affect human GH gene expression in transgenic mice in vivo.Endocrine connections · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
CCAAT/enhancer binding proteins (C/EBPs) regulate gene expression in a variety of cells/tissues/organs, during a range of developmental stages, under both physiological and pathological conditions. C/EBP-related transcription factors have a consensus binding specificity of 5'-TTG-CG-CAA-3', with a central CpG/CpG and two outer CpA/TpG dinucleotides. Methylation of the CpG and CpA sites generates a DNA element with every pyrimidine having a methyl group in the 5-carbon position (thymine or 5-methylcytosine (5mC)). To understand the effects of both CpG and CpA modification on a centrally-important transcription factor, we show that C/EBPβ binds the methylated 8-bp element with modestly-increased (2.4-fold) binding affinity relative to the unmodified cognate sequence, while cytosine hydroxymethylation (particularly at the CpA sites) substantially decreased binding affinity (36-fold). The structure of C/EBPβ DNA binding domain in complex with methylated DNA revealed that the methyl groups of the 5mCpA/TpG make van der Waals contacts with Val285 in C/EBPβ. Arg289 recognizes the central 5mCpG by forming a methyl-Arg-G triad, and its conformation is constrained by Val285 and the 5mCpG methyl group. We substituted Val285 with Ala (V285A) in an Ala-Val dipeptide, to mimic the conserved Ala-Ala in many members of the basic leucine-zipper family of transcription factors, important in gene regulation, cell proliferation and oncogenesis. The V285A variant demonstrated a 90-fold binding preference for methylated DNA (particularly 5mCpA methylation) over the unmodified sequence. The smaller side chain of Ala285 permits Arg289 to adopt two alternative conformations, to interact in a similar fashion with either the central 5mCpG or the TpG of the opposite strand. Significantly, the best-studied cis-regulatory elements in RNA polymerase II promoters and enhancers have variable sequences corresponding to the central CpG or reduced to a single G:C base pair, but retain a conserved outer CpA sequence. Our analyses suggest an important modification-dependent CpA recognition by basic leucine-zipper transcription factors.
Indexed as
Identifiers
What OpenQuestion holds
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.