Publications by authors named "Phillip Wyss"

Background: In mammals, Imprinting Control Regions (ICRs) regulate a subset of genes in a parent-of-origin-specific manner. In both human and mouse, previous studies identified a set of CpG-rich motifs occurring as clusters in ICRs and germline Differentially Methylated Regions (gDMRs). These motifs consist of the ZFP57 binding site (ZFBS) overlapping a subset of MLL binding units known as MLL morphemes.

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While MLL1 activates gene expression in most tissues, ZFP57 represses transcription. MLL1 selectively interacts with a group of nonmethylated DNA sequences known as the MLL1 morphemes. ZFP57 associates with a methylated hexamer (ZFBS), dispersed in the genomic DNA segments known as Imprinted Control Regions (ICRs) and germline Differentially Methylated Regions (gDMRs), to maintain allele-specific gene repression.

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Previous studies have shown that Mixed Lineage Leukemia 1 (MLL1 or MLL) binds a group of CpG-rich motifs known as morphemes. To examine whether occurrences of MLL1 morphemes in genomic DNA may influence codon utilization, we analyzed the frequency of various 9-mers in human cDNAs and in total human genomic DNA. We uncovered preferential utilization of GGC for Gly, GCG for Ala, CCG for Pro, and TCG for Ser, in coding sequences (CDSs) that included MLL1 morphemes.

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Background: Mixed Lineage Leukemia 1 (MLL1) is a mammalian ortholog of the Drosophila Trithorax. In Drosophila, Trithorax complexes transmit the memory of active genes to daughter cells through interactions with Trithorax Response Elements (TREs). However, despite their functional importance, nothing is known about sequence features that may act as TREs in mammalian genomic DNA.

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In Fourier transform mass spectrometry, it is well-known that plotting the spectrum in absorption mode rather than magnitude mode has several advantages. However, magnitude spectra remain commonplace due to difficulties associated with determining the phase of each frequency at the onset of data acquisition, which is required for generating absorption spectra. The phasing problem for electrostatic traps is much simpler than for Fourier transform ion cyclotron resonance (FTICR) instruments, which greatly simplifies the generation of absorption spectra.

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The 355 nm time-of-flight negative ion photoelectron spectra of (o-, m-, and p-chlorophenyl)nitrene radical anions are reported. Electron affinities are obtained from the photoelectron spectra, and are 1.79 +/- 0.

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We developed a computational model to explore the hypothesis that regulatory instructions are context dependent and conveyed through specific 'codes' in human genomic DNA. We provide examples of correlation of computational predictions to reported mapped DNase I hypersensitive segments in the HOXA locus in human chromosome 7. The examples show that statistically significant 9-mers from promoter regions may occur in sequences near and upstream of transcription initiation sites, in intronic regions, and within intergenic regions.

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A major challenge in systems biology is to discover and reconstruct the cis-regulatory networks through which the expression of genes is controlled. Even though a variety of sequences have been shown to interact with the transcription factors that bind DNA, extensive work is needed to discover and classify regulatory "codes" and to elucidate the role played by the sequence context of genomic DNA in the regulation of genes. Databases of sequence elements extracted from regulatory regions may facilitate this process.

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Discovery of lexical characteristics of specific sequence motifs in human genomic DNA can help with predicting and classifying regulatory cis elements according to the genes they control. In lexical models, some "words" may serve as downstream targets of signaling systems, whereas other "words" may specify sequences that selectively control the expression of a subset of genes to produce the various cell types and tissues. To discover lexical features of potential regulatory "words," we have created a database of 9-mers derived from the promoter regions of a subset of human protein-coding genes.

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Central to reconstruction of cis-regulatory networks is identification and classification of naturally occurring transcription factor-binding sites according to the genes that they control. We have examined salient characteristics of 9-mers that occur in various orders and combinations in the proximal promoters of human genes. In evaluations of a dataset derived with respect to experimentally defined transcription initiation sites, in some cases we observed a clear correspondence of highly ranked 9-mers with protein-binding sites in genomic DNA.

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