Scaffold-attached regions from the human interferon .beta. domain can be used to enhance the stable expression of genes under the control of various promoters

Klehr, D.; Maass, Karin; Bode, Jürgen

doi:10.1021/bi00219a015

Cited by 180 publications

(145 citation statements)

References 35 publications

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“…A transgene flanked by S/MAR elements may therefore constitute an autonomous chromatin domain whose expression would remain independent of the adjacent chromosomal environment. Consistent with this view, S/ MARs have been shown to increase the expression of adjacent transgenes when co-inserted into a chromosomal environment (Kalos and Fournier, 1995;Klehr et al, 1991;Phi-Van et al, 1990;Poljak et al, 1994). …”

Section: Introductionmentioning

confidence: 67%

Use of the chicken lysozyme 5′ matrix attachment region to generate high producer CHO cell lines

Girod

Zahn-Zabal

Mermod

2005

Biotechnol. Bioeng.

104

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Scaffold or matrix attachment region (S/MAR) genetic elements have previously been proposed to insulate transgenes from repressive effects linked to their site of integration within the host cell genome. We have evaluated their use in various stable transfection settings to increase the production of recombinant proteins such as monoclonal antibodies from Chinese hamster ovary (CHO) cell lines. Using the green fluorescent protein coding sequence, we show that S/MAR elements mediate a dual effect on the population of transfected cells. First, S/ MAR elements almost fully abolish the occurrence of cell clones that express little transgene that may result from transgene integration in an unfavorable chromosomal environment. Second, they increase the overall expression of the transgene over the whole range of expression levels, allowing the detection of cells with significantly higher levels of transgene expression. An optimal setting was identified as the addition of a S/MAR element both in cis (on the transgene expression vector) and in trans (co-transfected on a separate plasmid). When used to express immunoglobulins, the S/MAR element enabled cell clones with high and stable levels of expression to be isolated following the analysis of a few cell lines generated without transgene amplification procedures.

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Section: Introductionmentioning

confidence: 67%

Use of the chicken lysozyme 5′ matrix attachment region to generate high producer CHO cell lines

Girod

Zahn-Zabal

Mermod

2005

Biotechnol. Bioeng.

104

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“…These elements control gene expression by supposedly altering the chromosomal structure. Assessment of their regulatory function is therefore dependent upon the nucleosomal organization of the DNA (Klehr et al, 1991) and remains undetected in transient assays where naked DNA is examined. Madisen and Groudine (1994) showed that elements other than the Ca-enhancer were also necessary for c-myc deregulation in a murine mouse plasmacytoma.…”

Section: Discussionmentioning

confidence: 99%

Deregulation of the proto-oncogene c-myc through t(8;22) translocation in Burkitt's lymphoma

et al. 1999

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“…Matrix attachment regions (MARS), containing extensive runs of AT residues, have been shown to confer position and orientation independence to transcriptional properties of several genes in vitro and in vivo [Stief et al, 1989;Phi-Van and Stratling, 1990;Gasser et al, 1989;von Kries et al, 1991;Luderus et al, 1992;Klehr et al, 1991;Bonifer et al, 19901. These stable gene attachment sites mediate long-range influences covering several hundred kb [Jarman and Higgs, 19881.…”

Section: Introductionmentioning

confidence: 99%

Nuclear architecture supports integration of physiological regulatory signals for transcription of cell growth and tissue‐specific genes during osteoblast differentiation

Stein

Wijnen

Lian

et al. 1994

J of Cellular Biochemistry

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During the past several years it has become increasingly evident that the three-dimensional organization of the nucleus plays a critical role in transcriptional control. The principal theme of this prospect will be the contribution of nuclear structure to the regulation of gene expression as functionally related to development and maintenance of the osteoblast phenotype during establishment of bone tissue-like organization. The contributions of nuclear structure as it regulates and i s regulated by the progressive developmental expression of cell growth and bone cell related genes will be examined. We will consider signalling mechanisms that integrate the complex and interdependent responsiveness to physiological mediators of osteoblast proliferation and differentiation. The focus will be on the involvement of the nuclear matrix, chromatin structure, and nucleosome organization in transcriptional control of cell growth and bone cell related genes. Findings are presented which are consistent with involvement of nuclear structure in gene regulatory mechanisms which support osteoblast differentiation by addressing four principal questions: 1 ) Does the representation of nuclear matrix proteins reflect the developmental stage-specific requirements for modifications in transcription during osteoblast differentiation? 2 ) Are developmental stage-specific transcription factors components of nuclear matrix proteins? 3) Can the nuclear matrix facilitate interrelationships between physiological regulatory signals that control transcription and the integration of activities of multiple promoter regulatory elements? 4) Are alterations in gene expression and cell phenotypic properties in transformed osteoblasts and osteosarcoma cells reflected by modifications in nuclear matrix proteins? There is a striking representation of nuclear matrix proteins unique to cells, tissues as well as developmental stages of differentiation, and tissue organization. Together with selective association of regulatory molecules with the nuclear matrix in a growth and differentiation-specific manner, there is a potential for application of nuclear matrix proteins in tumor diagnosis, assessment of tumor progression, and prognosis of therapies where properties of the transformed state of cells is modified. It i s realistic to consider the utilization of nuclear matrix proteins for targeting regions of cell nuclei and specific genomic domains on the basis of developmental phenotypic properties or tissue pathology. z 1994 WlIey-Llss, Inc

show abstract

Scaffold-attached regions from the human interferon .beta. domain can be used to enhance the stable expression of genes under the control of various promoters

Cited by 180 publications

References 35 publications

Use of the chicken lysozyme 5′ matrix attachment region to generate high producer CHO cell lines

Use of the chicken lysozyme 5′ matrix attachment region to generate high producer CHO cell lines

Deregulation of the proto-oncogene c-myc through t(8;22) translocation in Burkitt's lymphoma

Nuclear architecture supports integration of physiological regulatory signals for transcription of cell growth and tissue‐specific genes during osteoblast differentiation

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