A nuclease-hypersensitive element of the human c-myc promoter interacts with a transcription initiation factor.

Postel, Edith H.; Flint, S. J.

doi:10.1128/mcb.9.11.5123

Cited by 148 publications

(124 citation statements)

References 50 publications

(67 reference statements)

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“…1A). This fragment contains the c-myc P 0 and P 1 promoters, several transcription factor consensus binding sites, and an organized nucleosome array stable with respect to chromosomal translocation (20,35,37,44,45,67,71,78,87). To analyze the effect of transcription on replicator activity, clonal cell lines were constructed using the yeast FLP recombinase to integrate donor plasmids containing wild-type or mutated versions of the c-myc core replicator in the FRT site in the HeLa/ 406 acceptor cell line (Fig.…”

Section: Resultsmentioning

confidence: 99%

Transcription Factor Binding and Induced Transcription Alter Chromosomal c-myc Replicator Activity

Ghosh

Liu

Randall

et al. 2004

Molecular and Cellular Biology

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The observation that transcriptionally active genes generally replicate early in S phase and observations of the interaction between transcription factors and replication proteins support the thesis that promoter elements may have a role in DNA replication. To test the relationship between transcription and replication we constructed HeLa cell lines in which inducible green fluorescent protein (GFP)-encoding genes replaced the proximal ϳ820-bp promoter region of the c-myc gene. Without the presence of an inducer, basal expression occurred from the GFP gene in either orientation and origin activity was restored to the mutant c-myc replicator. In contrast, replication initiation was repressed upon induction of transcription. When basal or induced transcription complexes were slowed by the presence of ␣-amanitin, origin activity depended on the orientation of the transcription unit. To test mechanistically whether basal transcription or transcription factor binding was sufficient for replication rescue by the uninduced GFP genes, a GAL4p binding cassette was used to replace all regulatory sequences within ϳ1,400 bp 5 to the c-myc gene. In these cells, expression of a CREB-GAL4 fusion protein restored replication origin activity. These results suggest that transcription factor binding can enhance replication origin activity and that high levels of expression or the persistence of transcription complexes can repress it.Models for DNA replication in eukaryotes derive significantly from studies of Saccharomyces cerevisiae and Xenopus laevis systems, in which prereplication complexes (pre-RCs) containing the hexameric origin recognition complex ORC, Cdc6, and the minichromosome maintenance proteins are activated by the cell cycle-regulated kinases Cdc7/Dbf4 and cyclin-dependent kinases to unwind DNA and load DNA polymerases for the initiation of DNA synthesis (reviewed in reference 8). Although replication origins in higher organisms do not generally display the conserved size, sequence, or structure of replicators in S. cerevisiae, this overall series of events appears to be conserved in fission yeast and metazoan somatic cells, and the demonstration that chromosomal regions involved in the initiation of replication can promote replication when transferred to ectopic chromosomal sites provides genetic evidence for the existence of defined replicator elements that can control replication initiation in the chromosomes of multicellular organisms (1,2,4,51,52).Replication origins are frequently found upstream of eucaryotic transcription units (reviewed in reference 57), consistent with the suggestion that transcription and replication may be oriented to coordinate transcription and replication fork movement (13,27,50). Transcribed sequences are generally replicated earlier in S phase in the cells where they are expressed than in cells where they are not (22,76), possibly as a result of the modification of chromatin structure by transcription factors (48). However, several investigators report positive (11,19,21,25,34,36,47...

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Section: Resultsmentioning

confidence: 99%

Transcription Factor Binding and Induced Transcription Alter Chromosomal c-myc Replicator Activity

Ghosh

Liu

Randall

et al. 2004

Molecular and Cellular Biology

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“…We (23), and H4TF-1 (5) have DNA recognition sites that are similar to those of suGF1 but have been shown to be proteins larger than 100 kDa. Other factors implicated in human c-myc gene regulation appear to differ from suGFl in that they do not result in a DNase I footprint on their G-rich recognition site (factor PuF [29]) or are associated with RNA (factor NSE [6]). The biochemical and DNA-binding properties of suGF1 are remarkably similar to those of BGP1, the chicken factor implicated in PA-globin gene expression (4,22).…”

Section: Figmentioning

confidence: 99%

“…We have shown that suGF1 has a DNA-binding specificity similar to those of several factors which recognize G-rich sequences within the context of pur. pyr stretches upstream of genes (6,9,12,24,29,34). In addition, several of these factors have been implicated in gene regulation via alterations in chromatin structure within the pur-pyr region (see the introduction).…”

Section: Figmentioning

confidence: 99%

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Purification of an oligo(dG).oligo(dC)-binding sea urchin nuclear protein, suGF1: a family of G-string factors involved in gene regulation during development.

Hapgood¹,

Patterton²

1994

Mol. Cell. Biol.

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Genes Dev.2: [863][864][865][866][867][868][869][870][871][872][873] 1988). We have purified a 59.5-kDa nuclear protein (suGF1) from sea urchin embryos by DNA affinity chromatography. suGF1 has high binding affinity and specificity for oligo(dG) -oligo(dC). The identity of the purified protein was confirmed by renaturation of sequence-specific DNA-binding activity from a sodium dodecyl sulfate-polyacrylamide gel slice and by Southwestern (DNA-protein) (4,19). In addition, G-string-binding factors have been detected in a number of different tissues from various organisms (8,19,22,38). The promoter of the chicken adult 3-globin gene contains a G string of 16 to 18 Gs (22, 28). There is strong evidence that regulation of expression of this gene involves a complex interplay between binding of a G-string factor, DNA conformation, and displacement of a positioned nucleosome at the G string (22). A G6 string has also been implicated in regulation of gene expression during sea urchin development via binding of a G-string factor to a cis-regulatory element present in the promoter of a cell lineage-specific gene LpS13 (38). This sea urchin G-string factor may be related to a putative mammalian transcription factor, IF1, implicated in the coordinate regulation of expression of the (xl (I) and a2 (I) collagen genes during embryonic development via binding to G7 strings present in both promoters (17, 38). Interestingly, a G7 string occurs within a purine-rich region of the chicken ct2(I) collagen gene promoter which is hypersensitive to Si nuclease and DNase I in chromatin in a tissuespecific fashion (24).G strings have in common with homopurine-homopyrimidine (pur. pyr) stretches the ability to form unusual DNA structures such as triple helices in vitro, the formation of which depends critically on the degree of superhelical stress of the DNA, the length of the homopurine stretch, and the chemical environment (21,36). Several authors have proposed that G strings may function in vivo as a conformational switch which is modulated in some way by G-stringbinding proteins (4,19,20,24).A similar role has been proposed for G-rich regions which occur within pur. pyr stretches upstream of several housekeeping genes such as the c-Ki-ras, epidermal growth factor receptor, and c-myc genes (6,12,14,23,29). These pur-pyr regions are S1 nuclease sensitive in vitro and bind to factors containing multiple copies of the sequence GGGNGGG in their DNA recognition sites. In some cases, alterations in chromatin structure correlating with the state of expression of these genes have been mapped to the pur. pyr regions in nuclei.These observations raise several unresolved issues. G strings may play a role in gene regulation during development via families of G-string factors with related functions. The structural and functional relationships among various G-string factors as well as factors binding to G-rich sequences within pur-pyr stretches need to be examined, considering the parallels that can be drawn between their proposed biological role...

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“…A variety of positive and negative elements has been identified within the regulatory region of the c-myc promoters with potential binding sites for the transcription factors NF1/CTF, SP1, E2F, Ap1, OCT, PRF, PuF, NFB, YY1, Maz, FBP, LR1, hu-CUT, CTCF, and others (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), for reviews, see Refs. 1 and 2.…”

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confidence: 99%

Nucleosomal Structure of Active and Inactive c-myc Genes

Pullner

Mautner²,

Albert³

et al. 1996

Journal of Biological Chemistry

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The nucleosomal structure of active and inactive cmyc genes has been analyzed in detail in undifferentiated and differentiated cells of the promyelocytic leukemia cell line HL60. The c-myc P2 promoter was never found in nucleosomal configuration, no matter whether c-myc was expressed or not. Differences in the nucleosomal structure, however, were found in the promoter upstream region proximal to a previously described DNase I-hypersensitive site I, at the P0 promoter, and at the P1 promoter and upstream thereof. In these regions nucleosomes were detected in differentiated but not undifferentiated HL60 cells. Similar patterns of nucleosomes as found for active and inactive c-myc genes in HL60 cells were found for active and inactive episomal c-myc genes in stably transfected B cell lines. In these cell lines three activation stages could be described for episomal c-myc constructs: (i) uninducible, (ii) inducible, and (iii) induced. Significant differences in the nucleosomal structure of c-myc were observed for the uninducible and inducible stages, but not for the inducible and induced stages.

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A nuclease-hypersensitive element of the human c-myc promoter interacts with a transcription initiation factor.

Cited by 148 publications

References 50 publications

Transcription Factor Binding and Induced Transcription Alter Chromosomal c-myc Replicator Activity

Transcription Factor Binding and Induced Transcription Alter Chromosomal c-myc Replicator Activity

Purification of an oligo(dG).oligo(dC)-binding sea urchin nuclear protein, suGF1: a family of G-string factors involved in gene regulation during development.

Nucleosomal Structure of Active and Inactive c-myc Genes

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