Prediction of cis-regulatory elements controlling genes differentially expressed by retinal and choroidal vascular endothelial cells

Cultured endothelial cells of the human retina and choroid demonstrate distinct patterns of gene expression. We hypothesized that differential gene expression reflected differences in the interactions of transcription factors and respective cis-regulatory motifs(s) in these two endothelial cell subpopulations, recognizing that motifs often exist as modules. We tested this hypothesis in silico by using TRANSFAC Professional and CisModule to identify cis-regulatory motifs and modules in genes that were differentially expressed by human retinal versus choroidal endothelial cells, as identified by analysis of a microarray data set. Motifs corresponding to eight transcription factors were significantly (p < 0.05) differentially abundant in genes that were relatively highly expressed in retinal (i.e., glucocorticoid receptor, high mobility group AT-hook 1, heat shock transcription factor 1, p53, vitamin D receptor) or choroidal (i.e., transcription factor E2F, Yin Yang 1, zinc finger 5) endothelial cells. Predicted cis-regulatory modules were quite different for these two groups of genes. Our findings raise the possibility of exploiting specific cis-regulatory motifs to target therapy at the ocular endothelial cells subtypes responsible for neovascular age-related macular degeneration or proliferative diabetic retinopathy

Distinct nonrandom patterns of chromosomal deletions in giant-cell lesions of bone

Cytogenetic analyses were performed on a bone giant cell reparative granuloma (GCRG) and on three bone giant cell tumors (GCT). The present GCRG case is the second to be described cytogenetically. A modal chromosome number of 46 was observed in all samples. Clonal chromosome abnormalities were detected in all cases. The numerical alterations most frequently observed involved the loss of chromosomes 17 and 18. Among the structural anomalies observed, there was preferential involvement of chromosomes 6 and 10. Three GCT cases presented del(10)(p13) and two cases presented del(6)(q25) (1 GCRG and 1 GCT). These breakpoints mapped on 10p and 6q may harbour genes of importance in the development of bone giant cell tumors