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

The human gene ZFP161 on 18p11.21-pter encodes a putative c-myc repressor and is homologous to murine Zfp161 (chr 17) and Zfp161-rs1 (X chr)

Sobek-Klocke I, Disque-Kochem C, Ronsiek M, et al. The human gene ZFP161 on 18p11.21-pter encodes a putative c-myc repressor and is homologous to murine Zfp161 (chr 17) and Zfp161-rs1 (X chr). Genomics. 1997;43(2):156-164.A clone from a lambda gt11 cDNA expression library of HeLa cells was isolated, sequenced, and shown to encode a new human zinc finger protein. The cDNA of the gene termed ZFP161 has an open reading frame of 1347 bp. The predicted protein comprises 449 amino acid residues and contains five zinc finger motifs of the Kruppel type near the C-terminus and a BTB/POZ domain in the N-terminal region. The protein is 98% homologous to a murine zinc finger protein, ZP5 (M. Numoto et al., 1993, Nucleic Acids Res. 21: 3767-3775), which is a putative transcriptional repressor of c-myc and exhibits growth-suppressive activity in mouse cell lines. Through the use of a panel of somatic cell hybrids for chromosomal assignment and DNAs of somatic cell hybrids containing a deleted chromosome 18 for fine mapping, the human gene ZFP161 was localized to 18p11.21-pter. Therefore, ZFP161 is a candidate gene by position for the holoprosencephaly type 4 gene, HPE4, which is involved in congenital malformations. With DNAs from an interspecific backcross, two homologous mouse genes, Zfp161 and Zfp161-rs1, were mapped to chromosome 17 and the X chromosome, respectively. Mapping of Zfp161 confirms and extends a region of homology between distal mouse chromosome 17 and human 18p. (C) 1997 Academic Press