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 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.
Laboratory of Molecular Biotechnology, Institute of Biotechnology, University of Lausanne, and Center for Biotechnology UNIL-EPFL, Lausanne, Switzerland.
Salina
S
Arope
Niamh
N
Harraghy
Milos
M
Pjanic
Nicolas
N
Mermod
D024509:3' Flanking Region; D024506:5' Flanking Region; D000818:Animals; D001482:Base Composition; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D018628:Gene Dosage; D015870:Gene Expression; D005786:Gene Expression Regulation; D023061:Gene Order; D020868:Gene Silencing; D006801:Humans; D045170:Matrix Attachment Regions / Q000235:genetics*; D014158:Transcription, Genetic; D019076:Transgenes
D002843:Chromatin