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Cited by 39Genomics and Chromatin DynamicsEpigenetics and DNA MethylationChromosomal and Genetic Variations

Molecular characterization of a human matrix attachment region epigenetic regulator

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Arope, Salina, Harraghy, Niamh, Pjanic, Milos, Mermod, Nicolas·2013·PLoS ONE
DOI 10.1371/journal.pone.0079262PMC PMC3828356
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Abstract

Matrix attachment regions (MAR) generally act as epigenetic regulatory sequences that increase gene expression, and they were proposed to partition chromosomes into loop-forming domains. However, their molecular mode of action remains poorly understood. Here, we assessed the possible contribution of the AT-rich core and adjacent transcription factor binding motifs to the transcription augmenting and anti-silencing effects of human MAR 1-68. Either flanking sequences together with the AT-rich core were required to obtain the full MAR effects. Shortened MAR derivatives retaining full MAR activity were constructed from combinations of the AT-rich sequence and multimerized transcription factor binding motifs, implying that both transcription factors and the AT-rich microsatellite sequence are required to mediate the MAR effect. Genomic analysis indicated that MAR AT-rich cores may be depleted of histones and enriched in RNA polymerase II, providing a molecular interpretation of their chromatin domain insulator and transcriptional augmentation activities.

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  • Because most epigenetic elements are composed of nucleosome depleted regions, they could contribute to inhibiting the propagation of an inactive chromatin state surrounding the transgene, serving as genetic boundaries.

    “Since most of these elements are composed of nucleosome depleted regions, this could also contribute to the inhibition of the propagation of an inactive chromatin state surrounding the transgene, serving as genetic boundaries (Arope et al., 2013;Harraghy et al., 2015).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Arope et al., 2013

    The Discussion (page not provided) proposes that nucleosome depletion over MARs can block heterochromatin propagation and protect adjacent transgenes from silencing. It does not establish that most epigenetic elements have nucleosome-depleted regions; its evidence and proposed mechanism concern MARs and promoters. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Arope, S., Harraghy, N., Pjanic, M., & Mermod, N.
Affiliations
École Polytechnique Fédérale de Lausanne (CH)
Corresponding author
Mermod, Nicolas
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-11-14
Volume
8
Issue
11
Pages
e79262
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0079262
PMC
PMC3828356
OpenAlex
W1967449169
Cited by
39
References
2
Citations by year
2025: 2 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 4 · 2014: 2
FWCI
1.51
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • SERVAL (Université de Lausanne) (submittedVersion, other-oa)
Funders
Kommission für Technologie und Innovation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
matrix attachment regions, epigenetic regulation, transcription factor binding motifs, chromatin insulators, chromatin looping, histone depletion, RNA polymerase II, gene silencing
MeSH terms
Animals, Base Composition, Cell Line, Chromatin, Gene Expression Regulation, Humans, Transcription, Genetic, Gene Expression, Gene Dosage, Transgenes, Gene Silencing, Gene Order, 5' Flanking Region, 3' Flanking Region, Epigenesis, Genetic, Matrix Attachment Regions

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