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First published online March 2, 2004
doi: 10.1242/10.1242/jcs.00976

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Chromatin loops are selectively anchored using scaffold/matrix-attachment regions

¹ Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48202, USA
² Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48202, USA
³ Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48202, USA
⁴ Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48202, USA
⁵ German Research Center for Biotechnology, RDIF/Epigenetic Regulation, Mascheroder Weg 1, 38124 Braunschweig, Germany
⁶ SeeDNA Biotech Inc, Windsor, ON N9A 4J2, Canada

^* Author for correspondence (e-mail: hheng{at}genetics.wayne.edu)

The biological significance of nuclear scaffold/matrix-attachment regions (S/MARs) remains a topic of long-standing interest. The key to understanding S/MAR behavior relies on determining the physical attributes of in vivo S/MARs and whether they serve as rigid or flexible chromatin loop anchors. To analyze S/MAR behavior, single and multiple copies of the S/MAR-containing constructs were introduced into various host genomes of transgenic mice and transfected cell lines. These in vivo integration events provided a system to study the association and integration patterns of each introduced S/MAR. By utilizing FISH to visualize directly the localization of S/MARs on the nuclear matrix or chromatin loop, we were able to assign specific attributes to the S/MAR. Surprisingly, when multiple-copy S/MARs were introduced they were selected and used as nuclear matrix anchors in a discriminatory manner, even though they all contained identical primary sequences. This selection process was probably mediated by S/MAR availability including binding strength and copy number, as reflected by the expression profiles and association of multi-copy tandem inserted constructs. Whereas S/MARs functioned as the mediators of loop attachment, they were used in a selective and dynamic fashion. Consequently, S/MAR anchors were necessary but not sufficient for chromatin loops to form. These observations reconcile many seemingly contradictory attributes previously associated with S/MARs.

Key words: Chromatin loop, Loop anchor, S/MAR, FISH, Gene expression, Chromosome structure

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