Molecular characterization of a human matrix attachment region epigenetic regulator

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...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e79262-e79262
Main Authors: Arope, Salina, Harraghy, Niamh, Pjanic, Milos, Mermod, Nicolas
Format: Article
Language:English
Subjects:
3' Flanking Region
5' Flanking Region
Analysis
Animals
Augmentation
Base Composition
Binding
Bioinformatics
Biotechnology
Cell Line
Chromatin
Chromatin - genetics
Chromatin - metabolism
Chromosomes
Cores
Deoxyribonucleic acid
Dihydrofolate reductase
DNA
DNA binding proteins
DNA-directed RNA polymerase
Epigenesis, Genetic
Epigenetic inheritance
Epigenetics
Gene Dosage
Gene Expression
Gene Expression Regulation
Gene Order
Gene sequencing
Gene Silencing
Gene therapy
Genes
Genetic research
Genomes
Genomic analysis
Genomics
Histones
Humans
Laboratories
Matrix attachment regions
Matrix Attachment Regions - genetics
Microsatellites
Mode of action
Proteins
Regulatory sequences
Ribonucleic acid
RNA
RNA polymerase
RNA polymerase II
Transcription (Genetics)
Transcription factors
Transcription, Genetic
Transgenes
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0079262