Correct transcription of an immunoglobulin κ gene requires an upstream fragment containing conserved sequence elements

Falkner, Falko G.; Zachau, Hans G.

doi:10.1038/310071a0

Cited by 641 publications

(431 citation statements)

References 47 publications

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“…However, when 10 393 Figure 2A and B, the sequence 5'-ATGCAAA-3' homologous to the immunoglobulin heavy chain enhancer (position 212 -206) is underlined, and the polyoma virus enhancer homology (P-motif, position 196-186) is boxed. References for the various sequence elements are as follows (see also text): LPV enhancer (Pawlita et al, 1985;Mosthaf et al, 1985); BK virus (BKV) enhancer (Rosenthal et al, 1983); Igx light chain enhancer (Picard and Schaffner, 1984;Queen and Stafford, 1984); consensus sequences of the upstream promoter elements of the immunoglobulin heavy (VH) and light (VL, opposite strand) chain genes (Falkner and Zachau, 1984;Parslow et al, 1984); Ig heavy chain enhancer (opposite strand, Ephrussi et al, 1985 and references therein; the star indicates the C complementary to the G protected against dimethylsulfate modification, see text); Xenopus Ul/U2 RNA genes (Mattaj et al, 1985;Ciiberto et al, 1985;Krol et al, 1985); polyoma virus enhancer (opposite strand, Veldman et al, 1985;Ruley and Fried, 1983). For comparison the ElA-like motif of the polyoma virus enhancer (Hearing and Shenk, 1983;Herbomel et al 1984) is shown.…”

Section: Resultsmentioning

confidence: 99%

Multiple sequence motifs are involved in SV40 enhancer function.

Zenke¹,

Grundström²,

Matthes³

et al. 1986

The EMBO Journal

493

322

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A systematic mutagenesis of the SV40 enhancer indicates that it spans -100 bp and is composed of at least two distinct DNA domains which exhibit very little enhancing activity on their own. Their association results in a 400-fold enhancement of transcription, virtually irrespective of their relative orientation and, to some extent, of the distance between them. Enhancer activity can also be generated by duplication of either domain. We show also that the activity of each domain is due to the presence of several specific sequence motifs. These motifs are found assorted in different combinations in other viral and cellular enhancers. Key words: transcription/site-directed mutagenesis/promoter/ RNA polymerase B(ll)/simian virus 40 1983;Lusky et al., 1983;Hearing and Shenk, 1983;Veldman et al., 1985). However, such enhancer consensus sequences occur in DNA segments without enhancer properties, and enhancer activity can be generated by duplicating DNA sequences without enhancer activity on their own (Weber et al., 1984;Swimmer and Shenk, 1984), thus questioning the real functional significance of these consensus sequences.Therefore, we decided to determine, at the nucleotide level, the DNA sequences essential for the activity of the prototype SV40 enhancer. Systematic deletions and point mutations have been constructed throughout the enhancer region and their effect on SV40 early transcription investigated in vivo, using a transient expression assay in HeLa cells. We show here that the SV40 enhancer encompasses a large DNA segment of -100 nucleotides containing the 72-bp sequence, but also extending further upstream. Furthermore, the present study reveals that the enhancer is composed of at least two distinct DNA domains which exhibit very little enhancing activity on their own. However, their association results in a dramatic 400-fold enhancement of transcription, virtually irrespective of their relative orientation and, to some extent, of the distance between them. Enhancer activity can also be generated by duplication of either domain. In addition, we show that the activity of each domain is due to the presence of several specific sequence motifs. Various assortments of these motifs are found in other viral and cellular enhancers, suggesting that enhancers are mosaics of a limited number of basic evolutionary related sequence motifs.

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Section: Resultsmentioning

confidence: 99%

Multiple sequence motifs are involved in SV40 enhancer function.

Zenke¹,

Grundström²,

Matthes³

et al. 1986

The EMBO Journal

493

322

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“…Oct4 (encoded by the Pou5f1 gene; reviewed in detail in 3) is a member of octamer‐binding (Oct) TFs, named after the octamer DNA motif with a consensus sequence ATGCAAAT 4, 5, 6, 7, 8. The POU DNA‐binding domain has a bipartite structure with two subdomains—the N‐terminal POU‐specific domain (POU S ) and C‐terminal POU homeodomain (POU HD )—which are connected by a flexible linker region of variable sequence and length among the POU factors 9.…”

Section: Introductionmentioning

confidence: 99%

Changing POU dimerization preferences converts Oct6 into a pluripotency inducer

Jerabek

et al. 2016

EMBO Reports

123

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The transcription factor Oct4 is a core component of molecular cocktails inducing pluripotent stem cells (iPSCs), while other members of the POU family cannot replace Oct4 with comparable efficiency. Rather, group III POU factors such as Oct6 induce neural lineages. Here, we sought to identify molecular features determining the differential DNA‐binding and reprogramming activity of Oct4 and Oct6. In enhancers of pluripotency genes, Oct4 cooperates with Sox2 on heterodimeric SoxOct elements. By re‐analyzing ChIP‐Seq data and performing dimerization assays, we found that Oct6 homodimerizes on palindromic OctOct more cooperatively and more stably than Oct4. Using structural and biochemical analyses, we identified a single amino acid directing binding to the respective DNA elements. A change in this amino acid decreases the ability of Oct4 to generate iPSCs, while the reverse mutation in Oct6 does not augment its reprogramming activity. Yet, with two additional amino acid exchanges, Oct6 acquires the ability to generate iPSCs and maintain pluripotency. Together, we demonstrate that cell type‐specific POU factor function is determined by select residues that affect DNA‐dependent dimerization.

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“…A horizontalline above an aa symbol indicates that an invariant amino acid has been replaced by another amino acid. A conserved pentekaidecanucleotide, the decanucleotide promoter (Falkner and Zachau, 1984), a TATA box and the hepta-and nonanucleotide boxes are underlined. The asterisk marks a stop codon.…”

Section: (D) Nucleotide Sequences Of Three Transposed V K Genesmentioning

confidence: 99%

Localization, analysis and evolution of transposed human immunoglobulin Vκ genes

Lötscher

Zimmer

Klopstock

et al. 1988

Gene

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SUMMARYThe localization of V", gene regions to chromosome 2, on which the K locus is located, and to other chromosomes is described. The V", genes that have been transposed to other chromosomes are called orphons. The finding of two new V", genes on chromosome 22 is reported. A V", 11 gene of this region and two V", I genes of the Chr 1 and the cos 118 regions were sequenced. The two V", I orphon sequences and two others that had been determined previously were 97.5% identical, indicating that they may have evolved from a common ancestor by amplification. A model of the evolution of the human V", orphons is discussed. INTRODucnONThe light chains of the K type of the human immunoglobulins are encoded by numerous V", gene segments and by one J ",-C", gene segment. Functional K genes are formed by recombination of one V", gene segment with J ",C", (for reviews, see

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Correct transcription of an immunoglobulin κ gene requires an upstream fragment containing conserved sequence elements

Cited by 641 publications

References 47 publications

Multiple sequence motifs are involved in SV40 enhancer function.

Multiple sequence motifs are involved in SV40 enhancer function.

Changing POU dimerization preferences converts Oct6 into a pluripotency inducer

Localization, analysis and evolution of transposed human immunoglobulin Vκ genes

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