A functional component of the sea urchin H2A gene modulator contains an extended sequence homology to a viral enhancer

Grosschedl, Rudolf; Mächler, M.; Rohrer, Urs Hoffmann; Birnstiel, Max L.

doi:10.1093/nar/11.23.8123

Cited by 30 publications

(26 citation statements)

References 41 publications

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“…4B, The most striking observation is that the USE 1 sequence is almost identical to the cis-acting element identified in the modulator of Ps. miliaris H2A gene by site-directed mutagenesis by Birnstiel and coworkers (23). Furthermore, the USE 2 sequence identified in this work overlaps with a conserved region that corresponds to the second functional domain, identified in the functional analysis by the same authors, in the Ps.…”

Section: Discussionsupporting

confidence: 54%

“…As shown in Fig. 4C, the USE 1 sequence corresponds to a highly conserved portion of the H2A flanking sequence, originally identified by Birnstiel and coworkers (23) the clone contains two tandem copies of the oligonucleotide in a head-to-tail arrangement. We next carried out a competition experiment by coinjecting Mr H2A tk-70 and pUC-USE 1 at different molar ratios into Xenopus oocytes.…”

Section: Dna-binding Proteins In the Sea Urchin Nuclear Extractmentioning

confidence: 91%

“…The 5' flanking region of this gene contains, upstream to the basal transcriptional elements, a sequence § that possesses sequence similarity to the modulator element present in a similar location in the early H2A gene of the closely related sea urchin species Psammechinus miliaris. Functional studies of the region containing this sequence, carried out by microinjection into Xenopus laevis oocytes, have shown that it contains positive cis-acting elements for H2A transcription, with enhancer activity (21)(22)(23). Further studies of the histone gene chromatin conformation later revealed that active transcription of the early H2A gene of both sea urchin species is related to the appearance of a nuclease hypersensitive site just at the border of the modulator (24,25).…”

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confidence: 99%

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Cis-acting elements of the sea urchin histone H2A modulator bind transcriptional factors.

Palla

Casano²,

Albanese³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Functional tests, performed by microinjection into Xenopus laevis oocytes, show that a DNA fragment containing the modulator of the early histone H2A gene of Paracentrotus lividus enhances transcription of a reporter gene when located, in the physiological orientation, upstream of the tk basal promoter. Gel retardation and DNase I footprinting assays further reveal that the H2A modulator contains at least two binding sites [upstream sequence elements 1 and 2 (USE 1 and USE 2)] for nuclear factors extracted from sea urchin embryos, which actively transcribe the early histone gene set. Interestingly, USE 1 is highly homologous to a cis-acting element previously identified in the H2A modulator of Psammechinus milians [Grosschedl, R., Machler, M., Rohrer, U. & Birnstiel, M. L. (1983) Nucleic Acids Res. 11, 8123-8136]. Finally, a cloned oligonucleotide containing the USE 1 sequence competes efficiently in Xenopus oocytes with the H2A modulator to prevent enhancement of transcription of the reporter gene. From these results, we conclude that USE 1 and perhaps USE 2 in the H2A modulator are upstream transcriptional elements that are recognized by trans-acting factors common to Xenopus and sea urchin.The sea urchin genome contains several histone gene families that encode the protein subtypes of sperm (S-type) and of cleavage, early, and late stage embryo (1). The synthesis of specific histone protein variants during development is the result of regulatory mechanisms that operate at both the transcriptional and posttranscriptional level (2). The early histone genes in all sea urchin species are tandemly repeated 300-600 times and are organized in quintets (3,4). Transcription of this gene set occurs upon meiotic maturation and soon after fertilization (5-7). Newly synthesized early histone mRNAs accumulate at the 32-to 128-cell stage. Their transcription is shut off in mesenchyme blastula embryos (8-10). The transition from a transcriptionally active to an inactive state of the early histone genes is accompanied by structural alterations of their chromatin arrangement (11-13).Molecular genetic analysis of many polymerase II promoters has revealed that optimal and accurate initiation of transcription requires a cooperative interaction of transacting factors with multiple cis-acting transcriptional elements (14)(15)(16)(17).Recent studies on the factors involved in the transcriptional control of the sea urchin histone H1 and H2B genes have identified basal and ontogenic transcriptional elements involved in the transition from early to late gene expression during development (18,19). Furthermore, they have shown that an embryo-specific repressor element, the CCAAT displacement factor, prevents the interaction of a positive trans-acting factor with the CCAAT box ofthe sperm-specific H2B-1 gene (20) and in so doing may block transcription in the embryo.We have focused our attention on the early H2A gene ofthe sea urchin Paracentrotus lividus for several reasons. The 5' flanking region of this gene contains, upstream...

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Section: Discussionsupporting

confidence: 54%

Section: Dna-binding Proteins In the Sea Urchin Nuclear Extractmentioning

confidence: 91%

mentioning

confidence: 99%

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Cis-acting elements of the sea urchin histone H2A modulator bind transcriptional factors.

Palla

Casano²,

Albanese³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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“…An enhancer element, termed modulator, is located in the 5 0 region. [12][13][14][15] The H2A enhancer, which has a bipartite structure 13,14 (and unpublished observations), contains a binding site for the MBF-1 transcription factor, a Krü ppel-like zinc finger protein. 15,16 MBF-1 is not a stage-specific transcription factor, in that its expression does not parallel the timing of expression of the a-H2A histone gene.…”

Section: Introductionmentioning

confidence: 92%

Down-regulation of Early Sea Urchin Histone H2A Gene Relies on cis Regulative Sequences Located in the 5′ and 3′ Regions and Including the Enhancer Blocker sns

Melfi

Alessandro

et al. 2004

Journal of Molecular Biology

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“…The story was bound to unfold, but most likely in smaller bits, step by step, rather than in one fell swoop. Harbingers included the mentioned studies in Pierre Chambon's and George Khoury's lab on the 72 bp repeats of SV40 (Benoist and Chambon, 1981;Gruss et al, 1981) as well as the bipolar 'modulator' DNA of Max Birnstiel and his super-PhD student Rudi Grosschedl (Grosschedl and Birnstiel, 1980b; see also Grosschedl and Birnstiel, 1982;Grosschedl et al, 1983). A later investigation in Giovanni Spinelli's lab identified typical enhancer properties in a subsegment of this modulator (Palla et al, 1994).…”

Section: Clairvoyants and Potential Discoverersmentioning

confidence: 99%

Enhancers, enhancers – from their discovery to today’s universe of transcription enhancers

Schaffner

2015

Biological Chemistry

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Transcriptional enhancers are short (200-1500 base pairs) DNA segments that are able to dramatically boost transcription from the promoter of a target gene. Originally discovered in simian virus 40 (SV40), a small DNA virus, transcription enhancers were soon also found in immunoglobulin genes and other cellular genes as key determinants of cell-type-specific gene expression. Enhancers can exert their effect over long distances of thousands, even hundreds of thousands of base pairs, either from upstream, downstream, or from within a transcription unit. The number of enhancers in eukaryotic genomes correlates with the complexity of the organism; a typical mammalian gene is likely controlled by several enhancers to fine-tune its expression at different developmental stages, in different cell types and in response to different signaling cues. Here, I provide a personal account of how enhancers were discovered more than 30 years ago, and also address the amazing development of the field since then.

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A functional component of the sea urchin H2A gene modulator contains an extended sequence homology to a viral enhancer

Cited by 30 publications

References 41 publications

Cis-acting elements of the sea urchin histone H2A modulator bind transcriptional factors.

Cis-acting elements of the sea urchin histone H2A modulator bind transcriptional factors.

Down-regulation of Early Sea Urchin Histone H2A Gene Relies on cis Regulative Sequences Located in the 5′ and 3′ Regions and Including the Enhancer Blocker sns

Enhancers, enhancers – from their discovery to today’s universe of transcription enhancers

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