ArticleGenes & development2002
The barrier function of an insulator couples high histone acetylation levels with specific protection of promoter DNA from methylation.
Article in Genes & development, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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
73 citing papers in PubMed, 179 citations in OpenAlex.
- A Ubiquitous Chromatin Opening Element and DNA Demethylation Facilitate Doxycycline-Controlled Expression during Differentiation and in Transgenic Mice.ACS synthetic biology · 2023Article
- The sound of silence: Transgene silencing in mammalian cell engineering.Cell systems · 2022Review
- Article
- Review
- Investigating the Barrier Activity of Novel, Human Enhancer-Blocking Chromatin Insulators for Hematopoietic Stem Cell Gene Therapy.Human gene therapy · 2021Article
- Article
- Epigenetic control of gene regulation during development and disease: A view from the retina.Progress in retinal and eye research · 2018Review
- Assembly PCR synthesis of optimally designed, compact, multi-responsive promoters suited to gene therapy application.Scientific reports · 2016Article
- Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains.Genome research · 2016Article
- Early-life physical activity reverses metabolic and Foxo1 epigenetic misregulation induced by gestational sleep disturbance.American journal of physiology. Regulatory, integrative and comparative physiology · 2015Article
- Epigenetic regulation of fetal globin gene expression in adult erythroid cells.Translational research : the journal of laboratory and clinical medicine · 2015Review
- An insulator element located at the cyclin B1 interacting protein 1 gene locus is highly conserved among mammalian species.PloS one · 2015Article
- Chromatin function modifying elements in an industrial antibody production platform--comparison of UCOE, MAR, STAR and cHS4 elements.PloS one · 2015Article
- Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages.Cell metabolism · 2014Article
- Article
- RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation.Nature structural & molecular biology · 2014Article
- Unstable expression of transgene is associated with the methylation of CAG promoter in the offspring from the same litter of homozygous transgenic mice.Molecular biology reports · 2014Article
- Epigenetic regulation of EMT: the Snail story.Current pharmaceutical design · 2014Review
- DNA methylation pattern as important epigenetic criterion in cancer.Genetics research international · 2013Review
- Prototypic chromatin insulator cHS4 protects retroviral transgene from silencing in Schistosoma mansoni.Transgenic research · 2012Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Stably integrated transgenes flanked by the chicken beta-globin HS4 insulator are protected against chromosomal position effects and gradual extinction of expression during long-term propagation in culture. To investigate the mechanism of action of this insulator, we used bisulfite genomic sequencing to examine the methylation of individual CpG sites within insulated transgenes, and compared this with patterns of histone acetylation. Surprisingly, although the histones of the entire insulated transgene are highly acetylated, only a specific region in the promoter, containing binding sites for erythroid-specific transcription factors, is highly protected from DNA methylation. This critical region is methylated in noninsulated and inactive lines. MBD3 and Mi-2, subunits of the Mi-2/NuRD repressor complex, are bound in vivo to these silenced noninsulated transgenes. In contrast, insulated cell lines do not show any enrichment of Mi-2/NuRD proteins very late in culture. In addition to the high levels of histone acetylation observed across the entire insulated transgene, significant peaks of H3 acetylation are present over the HS4 insulator elements. Targeted histone acetylation by the chicken beta-globin insulator occurs independently of gene transcription and does not require the presence of a functional enhancer. We suggest that this acetylation is in turn responsible for the maintenance of a region of unmethylated DNA over the promoter. Whereas DNA methylation often leads to histone deacetylation, here acetylation appears to prevent methylation.
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.