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We have mapped the chromosomal binding site distribution of a transcription factor in human cells. The NF-KB family of transcription factors plays an essential role in regulating the induction of genes involved in several physiological processes, including apoptosis, immunity, and inflammation. The binding sites of the NF-&key;B family member p65 were determined by using chromatin immunoprecipiration and a genomic microarray of human chromosome 22 DNA. Sites of binding were observed along the entire chromosome in both ceding and noncoding regions, with an enrichment at the 5' end of genes. Strikingly, a significant proportion of binding was seen in intronic regions, demonstrating that transcription factor binding is not restricted to promoter regions. NF-&key;B binding was also found at genes whose expression was regulated by tumor necrosis factor a, a known inducer of NF-&key;B-dependent gene expression, as well as adjacent to genes whose expression is not affected by tumor necrosis factor α. Many of these latter genes are either known to be activated by NF-&key;B under other conditions or are consistent with NF-&key;B's role in the immune and apoptotic responses. Our results suggest that binding is not restricted to promoter regions and that NF-&key;B binding occurs at a significant number of genes whose expression is not altered, thereby suggesting that binding alone is not sufficient for gene activation. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD), the most common cause of irreversible vision loss in individuals aged older than 50 years, is classified as either wet (neovascular) or dry (nonneovascular). Inherited variation in the complement factor H gene is a major risk factor for drusen in dry AMD. Here we report that a single-nucleotide polymorphism in the promoter region of HTRA1, a serine protease gene on chromosome 10q26, is a major genetic risk factor for wet AMD. A whole-genome association mapping strategy was applied to a Chinese population, yielding a P value of <10-11. Individuals with the risk-associated genotype were estimated to have a likelihood of developing wet AMD 10 times that of individuals with the wild-type genotype. [ABSTRACT FROM AUTHOR]

Studies the transcriptional activity of human Chromosome 22. Construction of the human Chromosome 22 DNA microarray; Expression of Chromosome 22 genes; Materials and methods; Discussion; Conclusion.