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      Induction of transcription within chromosomal DNA loops flanked by MAR elements causes an association of loop DNA with the nuclear matrix

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          Abstract

          The spatial organization of an ∼170 kb region of human chromosome 19, including CD22 and GPR40–GPR43 genes, was studied using in situ hybridization of a set of cosmid and PAC probes with nuclear halos prepared from proliferating and differentiated HL60 cells. The whole region under study was found to be looped out into the nuclear halo in proliferating cells. It is likely that the loop observed was attached to the nuclear matrix via MAR elements present at the flanks of the area under study. Upon dimethyl sulfoxide-induced differentiation of the cells the looped fragment became associated with the nuclear matrix. This change in the spatial organization correlated with the activation of transcription of at least two ( CD22 and GPR43) genes present within the loop. The data obtained are discussed in the framework of the hypothesis postulating that the spatial organization of chromosomal DNA is maintained via constitutive (basic) and facultative (transcription-related) interactions of the latter with the nuclear matrix.

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          The structure of histone-depleted metaphase chromosomes.

          J Paulson, U K Laemmli (1977)
          Article 0 comments Cited 123 times – based on 0 reviews     Review now
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            Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites.

            P Cockerill, James W Garrard (1986)
            Introduction of torsional stress into active chromatin domains requires that linear DNA molecules be anchored in vivo to impede free rotation. While searching for these anchorage elements, we have localized a nuclear matrix association region (MAR) within the mouse immunoglobulin kappa gene that contains two topoisomerase II sites and is adjacent to the tissue-specific enhancer. The same matrix contact occurs when the kappa locus is in germ-line (inactive) or rear-ranged (transcribed) configurations. This constitutive anchorage site partitions the gene into V-J and C region chromatin domains. We demonstrate that at least 10,000 similar and evolutionarily conserved MAR binding sites exist in the nucleus. We propose that these sites, in association with topoisomerase II and possibly in conjunction with enhancers, play fundamental roles in the functional organization of chromatin loop domains.
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              Chromatin loops are selectively anchored using scaffold/matrix-attachment regions.

              J. Ye, Stephen A. Krawetz, Alan B. Stevens … (2004)
              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.
              Article 0 comments Cited 48 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nucleic Acids Res
                Journal ID (publisher-id): Nucleic Acids Research
                Title: Nucleic Acids Research
                Publisher: Oxford University Press
                ISSN (Print): 0305-1048
                ISSN (Electronic): 1362-4962
                Publication date Collection: 2005
                Publication date (Print): 2005
                Publication date (Electronic): 26 July 2005
                Volume: 33
                Issue: 13
                Pages: 4157-4163
                Affiliations
                Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology RAS Vavilov Street 34/5, 117984 Moscow, Russia
                1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS 117997 Moscow, Russia
                Author notes
                *To whom correspondence should be addressed. Tel: +7 95 135 30 92; Fax: +7 95 135 41 05; Email: sergey.v.razin@ 123456usa.net
                Article
                DOI: 10.1093/nar/gki733
                PMC ID: 1180747
                PubMed ID: 16049024
                SO-VID: 85154772-bd1b-47bf-b55c-456260a1251e
                Copyright © © The Author 2005. Published by Oxford University Press. All rights reserved
                License:

                The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@ 123456oupjournals.org

                History
                Date received : 19 May 2005
                Date revision received : 23 June 2005
                Date accepted : 08 July 2005
                Categories
                Subject: Article

                ScienceOpen disciplines: Genetics
                Data availability:
                ScienceOpen disciplines: Genetics

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