Experimental analysis and computer prediction of CTF/NFI transcription factor DNA binding sites 1 1Edited by M. Yaniv

Roulet, E.; Bucher, Philippe; Schneider, Ralf; Wingender, Edgar; Dusserre, Yves; Werner, Thomas; Mermod, Nicolas

doi:10.1006/jmbi.2000.3614

Cited by 66 publications

(49 citation statements)

References 45 publications

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“…Alignment of the 14 sequences revealed a consensus sequence of TTGGCA(N) 3 TGCCAA, which is nearly identical to the binding sequence reported previously for vertebrate NFIs [TTGGC-(N) 5 GCCAA] (Fig. 1A) (see Materials and Methods) (10). The C. elegans consensus appears to have additional specificity at nucleotides 8 and 12, which flank the central spacer region (Fig.…”

Section: Resultssupporting

confidence: 77%

“…Previous studies of NFI-binding specificity used direct affinity isolation of transcription factor binding sites from the human genome (8), selection on oligonucleotide libraries (9), or bioinformatic comparison of motifs held in common by the promoters of putative NFI-regulated genes (10). NFI proteins have been linked to chromatin because both NFI and glucocorticoid receptor (GR) binding influence mouse mammary tumor virus (MMTV) promoter chromatin structure (11), and NFI proteins have functional and physical interactions with histones H1 and H3 (12,13).…”

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confidence: 99%

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DNA-binding specificity and in vivo targets of Caenorhabditis elegans nuclear factor I

Whittle

Lazakovitch

Gronostajski

et al. 2009

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

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The conserved nuclear factor I (NFI) family of transcription factors is unique to animals and essential for mammalian development. The Caenorhabditis elegans genome encodes a single NFI family member, whereas vertebrate genomes encode 4 distinct NFI protein subtypes (A, B, C, and X). NFI-1-deficient worms exhibit abnormalities, including reduced lifespan, defects in movement and pharyngeal pumping, and delayed egg-laying. To explore the functional basis of these phenotypes, we sought to comprehensively identify NFI-1-bound loci in C. elegans . We first established NFI-1 DNA-binding specificity using an in vitro DNA-selection strategy. Analysis yielded a consensus motif of TTGGCA(N) 3 TGCCAA, which occurs 586 times in the genome, a 100-fold higher frequency than expected. We next asked which sites were occupied by NFI-1 in vivo by performing chromatin immunoprecipitation of NFI-1 followed by microarray hybridization. Only 55 genomic locations were identified, an unexpectedly small target set. In vivo NFI-1 binding sites tend to be upstream of genes involved in core cellular processes, such as chromatin remodeling, mRNA splicing, and translation. Remarkably, 59 out of 70 (84%) of the C. briggsae orthologs of the identified targets contain conserved NFI binding sites in their promoters. These experiments provide a foundation for understanding how NFI-1 is recruited to unexpectedly few in vivo sites to perform its developmental functions, despite a vast over-representation of its binding motif.

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Section: Resultssupporting

confidence: 77%

mentioning

confidence: 99%

DNA-binding specificity and in vivo targets of Caenorhabditis elegans nuclear factor I

Whittle

Lazakovitch

Gronostajski

et al. 2009

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

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“…The nucleotide change at -374 resulting from a T-to-A substitution disrupts the binding of a variety of CTF/NF1 transcription factors established from the TRANSFAC database (24). A number of these proteins have been demonstrated to be involved in negative and positive gene regulation (25). Further studies are thus required to investigate whether these polymorphisms influence increased RAGE expression and whether this relates to the development of vascular disease in diabetes.…”

Section: Discussionmentioning

confidence: 99%

Effects of Novel Polymorphisms in the RAGE Gene on Transcriptional Regulation and Their Association With Diabetic Retinopathy

et al. 2001

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Interactions between advanced glycation end products (AGEs) and the receptor for AGE (RAGE) are implicated in the vascular complications in diabetes. We have identified eight novel polymorphisms, of which the ؊1420 (GGT)n, ؊1393 G/T, ؊1390 G/T, and ؊1202 G/A were in the overlapping PBX2 3 untranslated region (UTR), and the ؊429 T/C (66.5% TT, 33.5% TC/CC), ؊407 to -345 deletion (99% I, 1% I/D, 0% D), ؊374 T/A (66.4% TT, 33.6% TA/AA), and ؉20 T/A were in the RAGE promoter. To evaluate the effects on transcriptional activity, we measured chloramphenicol acetyl transferase (CAT) reporter gene expression, driven by variants of the -738 to ؉49 RAGE gene fragment containing the four polymorphisms identified close to the transcriptional start site. The -429 C, ؊374 A, and 63-bp deletion alleles resulted in a mean increase of CAT expression of twofold (P < 0.0001), threefold (P < 0.001), and fourfold (P < 0.05), respectively, with the -374 T and A alleles yielding highly differential binding of nuclear protein extract from both monocyte-and hepatocyte-derived cell lines. The prevalence of the functional polymorphisms were investigated in subjects with type 2 diabetes (106 with and 109 without retinopathy), with the -429 C allele showing an increase in the retinopathy group (P < 0.05). These data suggest that the polymorphisms involved in differences in RAGE gene regulation may influence the pathogenesis of diabetic vascular complications. Diabetes 50:1505-1511, 2001

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“…They normally describe only fixed-length motifs, whereas some DNA-binding proteins can bind to variable length sites (11). Finally, it is not always possible to construct a multiple alignment of binding sites, because there may be no consistent choice for the sequences' orientations such that every pair of sequences is optimally aligned.…”

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confidence: 99%

Quantitative prediction of NF-κB DNA– protein interactions

Udalova

Mott²,

Field³

et al. 2002

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

103

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We describe a general method based on principal coordinates analysis to predict the effects of single-nucleotide polymorphisms within regulatory sequences on DNA-protein interactions. We use binding data for the transcription factor NF-B as a test system. The method incorporates the effects of interactions between base pair positions in the binding site, and we demonstrate that such interactions are present for NF-B. Prediction accuracy is higher than with profile models, confirmed by crossvalidation and by the experimental verification of our predictions for additional sequences. The binding affinities of all potential NF-B sites on human chromosome 22, together with the effects of known single-nucleotide polymorphisms, are calculated to determine likely functional variants. We propose that this approach may be valuable, either on its own or in combination with other methods, when standard profile models are disadvantaged by complex internucleotide interactions.

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Experimental analysis and computer prediction of CTF/NFI transcription factor DNA binding sites 1 1Edited by M. Yaniv

Cited by 66 publications

References 45 publications

DNA-binding specificity and in vivo targets of Caenorhabditis elegans nuclear factor I

DNA-binding specificity and in vivo targets of Caenorhabditis elegans nuclear factor I

Effects of Novel Polymorphisms in the RAGE Gene on Transcriptional Regulation and Their Association With Diabetic Retinopathy

Quantitative prediction of NF-κB DNA– protein interactions

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