Biomedical subjects

Santa Jeremy Ono

Publications and source records attributed to Santa Jeremy Ono.

21 records · Page 2Linked to original sources

PubMed2002

Genomics and proteomics of allergic disease.

The world-wide effort to identify susceptibility genes for allergic diseases is motivated by the conviction that the identification of disease genes may permit the design of new classes of anti-inflammatory compounds. Molecules concerned with the allergic reaction, such as cytokines, chemokines, their receptors, major histocompatibility complex molecules, and transcription factors, could provide the candidate genes of the allergic diseases. On the basis of genetic studies, multiple research groups have attempted to identify a susceptibility gene for allergy using the candidate gene approach and/or genome-wide screening. Both of these approaches suggest genetic heterogeneity of allergic diseases. Many variants of candidate genes are or are not associated with particular diseases in different ethnic groups and the function of variants is now being investigated. Based on the information accumulated thus far and the information on the human genome sequence, future advances in research on genetic factors for allergic diseases will be likely lead to the establishment of more effective prophylaxis and therapy for these diseases.

Chemokines, CC↗

PubMed2002

Transcriptional regulation of the BCL-6 gene: mechanistic dissection using mutant cell lines.

BACKGROUND: Mice lacking the BCL-6 gene product exhibit overexpression of T helper cell type 2 cytokines, and multi-organ inflammatory responses characterized by eosinophilia and infiltration by IgE+ B lymphocytes. Elevated IgE levels appear to result from loss of BCL-6's role in repression of the Stat6-dependent processes of I-epsilon transcription and IgE class-switching. Understanding the regulation of the BCL-6 gene expression is therefore relevant to the allergic response, due to the IgE-dependent activation of mast cells and basophils. MATERIALS AND METHODS: We analyzed a pair of isogenic cell lines that exhibit differential expression of the BCL-6 gene and mapped the control point to transcription using nuclear run-on assays. Direct analyses of the BCL-6 gene and transfection experiments were carried out to map the molecular basis for the differential expression. RESULTS: In this study, we report that pair of isogenic cell lines exhibits differential expression of BCL-6. BCL-6 mRNA is barely detectable in Jijoye, a Burkitt lymphoma B cell line, but is abundant in Clone-13, a mutant cell line derived from Jijoye. Corresponding to the mRNA level, BCL-6 protein is detected only in Clone-13, but not in Jijoye. Nuclear run-on assays indicate that BCL-6 expression is regulated mainly at the transcriptional level in these two cell lines. Gene structural alterations are not detected in a region including a 3-kb promoter and the first intron, where most of the chromosomal translocations are observed in diffuse large cell lymphoma (DLCL). Interestingly, multiple, heterozygous point mutations are identified in the first intron, the hypermutation region of BCL-6, in both of the two cell lines. However, in transient transfection experiments these mutations have no effects on gene expression. CONCLUSIONS: Our data suggest that the distinct profile of BCL-6 expression in Jijoye/Clone-13 is due to either a missing negative element in a different portion of the gene or that there is an issue of chromatin accessibility operating in BCL-6 gene regulation. This pair of isogenic cell lines (Jijoye/Clone-13) thus provides a new system to dissect the regulation of BCL-6 gene expression.

Cell Line↗

PubMedDate not supplied

Derepression of HMGA2 gene expression in retinoblastoma is associated with cell proliferation.

To assess whether retinoblastoma formation is associated with the expression of high mobility group (HMG) A2 protein, a transcription factor that is highly expressed during embryogenesis and completely repressed in normal adult tissues, we performed Northern and Western blots and RT-PCR analyses, and immunohistochemistry to test for HMGA2 expression. We used established retinoblastoma cell lines in tumors grown in nude mice and clinical retinoblastoma specimens, and contrasted these tumors with normal embryonic and adult retina. Adenoviral-mediated antisense experiments were conducted on the retinoblastoma cell lines to suppress HMGA2 expression and determine if cell proliferation is HMGA2-dependent. We also transfected a retinoblastoma cell line to identify cis-regulatory elements and transcription initiation sites on the HMGA2 gene promoter. HMGA2 gene expression was silenced in terminally differentiated retina of 6-wk-old mice, but it was detected in retina of a 13.5-d postcoitum embryo. Reactivation of HMGA2 gene expression was observed in the retinoblastoma cell lines Y79, WERI-Rb1, and TOTL-1, in tumors derived from some of these cells propagated in nude mice, and in a high frequency of retinoblastomas excised from human patients. This suggests that expression of HMGA2 gene in retinoblastoma cells involves a derepression process. By using an antisense approach to block HMGA2 expression, we observed a decrease in the number of proliferating retinoblastoma cells. As a 1st step toward understanding HMGA2 gene reactivation in retinoblastoma, we mapped the 2 transcription initiation sites and associated positive regulatory elements within the WERI-Rb1 cells. Our discovery of derepression of HMGA2 gene expression in retinoblastoma provides the 1st evidence that this protein might contribute to neoplastic transformation of retina cells.

Animals↗