Biomedical subjects

Elsie I Pares-Matos

Publications and source records attributed to Elsie I Pares-Matos.

3 recordsLinked to original sources

PubMed2006

Exploring transcription factor binding properties of several non-coding DNA sequence elements in the human NF-IL6 gene.

We examined several DNA segments upstream of the transcription start site of the human NF-IL6 gene to evaluate the predictions of two computational models developed to identify potential regulatory elements in the non-coding regions of genes. One model, comparative genomics, is based on the hypothesis that functional regulatory sequences can be localized in alignments of genomic DNA from several species. The other model is based on the hypothesis that protein-binding sites in genomic DNA may include sequence elements that occur frequently in proximal promoters of genes. The segments selected for DNA binding and functional evaluations included: (1) two conserved regions identified in multi-species sequence alignments; (2) a region containing several localized hits with 9-mers that ranked highly in studies of proximal promoters of human genes; and (3) two regions that were either GC-rich and/or contained tracts of G. The assays were done under nearly identical experimental conditions, using a cell line (U937) representing human monocytes/macrophages. The experiments also aimed at evaluating what effect, if any, cellular stimulation could have on the interactions of nuclear proteins with naturally occurring GC-rich elements in a human genomic DNA. In DNA binding assays, several complexes were formed with the conserved regions identified in multi-species sequence alignment. Furthermore, these regions were active in functional assays. The region containing several matches with 9-mers derived from proximal promoters of human genes was not conserved but formed several complexes with nuclear proteins including Sp1, Egr-1, and an unidentified protein. In addition, this region was active in functional assays and responded to cellular stimulations. Overall, the results of the assays suggest an important role for the sequence context of genomic DNA in protein binding and selection.

Animals↗

PubMed2004

Exploring the characteristics of sequence elements in proximal promoters of human genes.

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. Evaluations of the larger dataset, derived with respect to the 5' end of human ESTs, revealed that a subset of the highly ranked 9-mers corresponded to sites for several known transcription factor families (including CREB, ETS, EGR-1, SP1, KLF, MAZ, HIF-1, and STATs) that play important roles in the regulation of vertebrate genes. We identified several highly ranked CpG-containing 9-mers, defining sites for interactions with the CREB and ETS families of proteins, and identified potential target genes for these proteins. The results of the studies imply that the CpG-containing transcription factor-binding sites regulate the expression of genes with important roles in pathways leading to cell-type-specific gene expression and pathways controlled by the complex networks of signaling systems.

5' Untranslated Regions↗

PubMed2002

Organization of the promoter region of the human NF-IL6 gene.

In monocyte/macrophages, the human NF-IL6 gene was activated by LPS or PMA. However, a robust response required stimulation of cells with both LPS and PMA. To examine the molecular basis of this response, we isolated human genomic DNA and determined the nucleotide sequence of a segment (6.4 kb) that included the transcription initiation site of the gene. The unique sequences in the 6.4-kb DNA include several potential transcription factor-binding elements that may explain the molecular basis of the activation of the human NF-IL6 gene by signaling molecules that control the immune and inflammatory responses. Deletion analysis localized an LPS+PMA responsive region downstream position -287, with respect to the transcription initiation site of the NF-IL6 gene. The responsive region includes a potential site for interactions with CREB and a region (-287 to -247) that interacts with SP1 and SP3. In functional assays, the potential CREB site responded to cellular stimulation. The region that interacted with SP1 and SP3 augmented the overall level of activity produced in response to LPS+PMA.

Binding Sites↗