Chromatin structure and protein binding in the putative regulatory region of the c-myc gene in burkitt lymphoma

doi:10.1016/0092-8674(84)90368-4

Cell

Volume 37, Issue 2, June 1984, Pages 381-391

https://doi.org/10.1016/0092-8674(84)90368-4 Get rights and content

Abstract

A chromosomal myc gene displays one of three patterns of activity depending upon the arrangement of the gene and its allelic partner. In nonmalignant B cells both myc alleles are normally expressed. In Burkitt lymphoma cells carrying both a translocated and a nontranslocated myc allele, the translocated allele is inappropriately expressed, while the non-translocated allele is virtually inactive. Here we examine the chromatin structure of these genes using DNAase I hypersensitivity in nonmalignant lymphoblastoid cells and in the Burkitt lymphoma, BL31. Three hypersensitivity patterns emerge that correlate with the state of the gene and reveal sites associated with putative regulatory structures. One region is associated with the two myc promoters, one with a specific nuclear protein binding site, and one—which is markedly enhanced in the inactive germline gene in the Burkitt cell—with a putative negative control region. The perturbation of the normal pattern in this particular Burkitt cell may be due to the action of an immunoglobulin enhancer.

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It is worth to note that several concerns are still present on the relevance of one single form in controlling the overall transcription process. Indeed, NHE III1 contains more G-tracts than those considered in the Pu27 fragment: in principle, all of them can be involved in the formation of secondary structures with different effects on gene transcription [24,34,35]. In addition, it is not possible to rule out that the cellular environments, as well as the insertion of the G-rich tract into a long nucleic acid context, can actually promote the formation of G-tetrads deriving from the pairing of different guanines in comparison to those identified in a short single stranded sequence.
G-rich sequences undergo unique structural equilibria to form G-quadruplexes (G4) both in vitro and in cell systems. Several pathologies emerged to be directly related to G4 occurrence at defined genomic portions. Additionally, G-rich sequences are significantly represented around transcription start sites (TSS) thus leading to the hypothesis of a gene regulatory function for G4. Thus, the tuning of G4 formation has been proposed as a new powerful tool to regulate gene expression to treat related pathologies. However, up-to date this approach did not provide any new really efficient treatment.
Here, we summarize the most recent advances on the correlation between the structural features of G4 in human promoters and the role these systems physiologically exert. In particular we focus on the effect of G4 localization among cell compartments and along the promoters in correlation with protein interaction networks and epigenetic state. Finally the intrinsic structural features of G4 at promoters are discussed to unveil the contribution of different G4 structural modules in this complex architecture.
It emerges that G4s play several roles in the intriguing and complex mechanism of gene expression, being able to produce opposite effects on the same target. This reflects the occurrence of a highly variegate network of several components working simultaneously.
The resulting picture is still fuzzy but some points of strength are definitely emerging, which prompts all of us to strengthen our efforts in view of a selective control of gene expression through G4 modulation. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.
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^†: Present Address: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20205.

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ArticleChromatin structure and protein binding in the putative regulatory region of the c-myc gene in burkitt lymphoma

Abstract

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J. Mol. Biol.

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J. Mol. Biol.

Cell

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Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma

The human c-myc oncogene: structural consequences of translocation into the IgH in Burkitt lymphoma

Cell

Generation of adenovirus by transfection of plasmids

Nucl. Acids Res.

Sequence of the murine and human cellular myc oncogenes and two modes of myc transcription resulting from chromosome translocation in B lymphoid tumors

EMBO J.

Cellular oncogenes and retroviruses

Ann. Rev. Biochem.

Structure and function of the promoter-enhancer region of polyoma and SV40

Amplification of endogenous myc-related DNA sequences in a human myeloid leukemia cell line

Nature

Interchromosomal recombination of the cellular oncogene c-myc with the immunoglobulin heavy chain locus in murine plasmacytomas is a reciprocal exchange

EMBO J.

Onc gene amplification in promyelocytic leukemia cell line HL-60 and primary leukaemic cells of the same patient

Nature

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Article
Chromatin structure and protein binding in the putative regulatory region of the c-myc gene in burkitt lymphoma