CpG island libraries from human Chromosomes 18 and 22: landmarks for novel genes

Cross, Sally H.; Clark, Victoria H.; Simmen, Martin W.; Bickmore, Wendy A.; Maroon, Habib; Langford, Cordelia; Carter, Nigel P.; Bird, Adrian

doi:10.1007/s003350010071

Cited by 28 publications

(22 citation statements)

References 3 publications

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“…Nevertheless, we proceeded to utilize CGI arrays for three reasons. First, while chromosome 22 contains many CpG islands, chromosome 21 has relatively few (11,12). The proximity of p53BS to CGIs might be more accurately determined within a broader survey of CGIs in the human genome.…”

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Functional Analysis of p53 Binding under Differential Stresses

Krieg

Hammond

Giaccia

2006

Molecular and Cellular Biology

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Hypoxia and DNA damage stabilize the p53 protein, but the subsequent effect that each stress has on transcriptional regulation of known p53 target genes is variable. We have used chromatin immunoprecipitation followed by CpG island (CGI) microarray hybridization to identify promoters bound by p53 under both DNA-damaging and non-DNA-damaging conditions in HCT116 cells. Using gene-specific PCR analysis, we have verified an association with CGIs of the highest enrichment (>2.5-fold) (REV3L, XPMC2H, HNRPUL1, TOR1AIP1, glutathione peroxidase 1, and SCFD2), with CGIs of intermediate enrichment (>2.2-fold) (COX7A2L, SYVN1, and JAG2), and with CGIs of low enrichment (>2.0-fold) (MYC and PCNA). We found little difference in promoter binding when p53 is stabilized by these two distinctly different stresses. However, expression of these genes varies a great deal: while a few genes exhibit classical induction with adriamycin, the majority of the genes are unchanged or are mildly repressed by either hypoxia or adriamycin. Further analysis using p53 mutated in the core DNA binding domain revealed that the interaction of p53 with CGIs may be occurring through both sequence-dependent and -independent mechanisms. Taken together, these experiments describe the identification of novel p53 target genes and the subsequent discovery of distinctly different expression phenomena for p53 target genes under different stress scenarios.The tumor microenvironment is a major factor influencing tumor growth, metastatic potential, and response to chemotherapeutic drugs and radiation therapy (7). The hypoxia-inducible factor (HIF) family of transcription factors regulates the expression of key enzymes in anaerobic glycolysis and proangiogenic factors (i.e., vascular endothelial growth factor), aiding cells in adapting to a low-oxygen environment (15). Thus, a tumor adapts to hypoxia first by sustaining itself via anaerobic metabolism and then by stimulating angiogenesis to acquire more nutrients and oxygen. However, the resulting vasculature tends to have aberrant structures with irregular blood flow and leaky walls, paradoxically creating regions of transient hypoxia and reoxygenation (76). Reoxygenation after hypoxia causes DNA damage, exacerbating genomic instability (25). The porous structure of the tumor vasculature may also provide an escape route for metastasizing cells. Repeated cycles of hypoxia, vascular formation, and reoxygenation select for cells that are more likely to survive in a restrictive environment. The consequences of this process are cancer cells that are more aggressive, more likely to metastasize, and more likely to be resistant to radiation and chemotherapy. Intimately tied to this process is the selection for cells that have lost the expression of functional p53 (19).A variety of cellular stresses, including DNA damage, oncogenic transformation, and hypoxia, stabilize the p53 protein by activating a host of stress-inducible kinases that phosphorylate p53 and MDM2, resulting in increased levels of p53 (17). Stabilized ...

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confidence: 99%

Functional Analysis of p53 Binding under Differential Stresses

Krieg

Hammond

Giaccia

2006

Molecular and Cellular Biology

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“…However, a GC-box as well as recognition sites for the rare cutter enzyme BssHII were found in the upstream region and in exon 1. The fact that the 5' region has a CG content over 60% indicates that CDCP1 contains a CpG island (Bird, 1986;Cross et al, 2000).…”

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Identification of a novel gene, CDCP1, overexpressed in human colorectal cancer

et al. 2001

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“…An early study has indicated that content of CpG islands in human genome is chromosomedependent, with that Chr 18 is CpG island poor and Chr 22 CpG island rich (Cross et al, 2000). Recently, Antequera (Antequera, 2003) found that content of CpG islands in human genome is gene-dependent.…”

Section: Discussionmentioning

confidence: 99%

“…CpG islands located in the gene PPRs play important roles in the reorganization of chromatin during mammalian spermiogenesis (Kundu and Rao, 1999) and in gene silencing during processes such as X-chromosome inactivation, imprinting, and silencing of intragenomic parasites (Takai and Jones, 2002). CpG islands are identified at the 5' end of approximately 60% of human genes and so are important genomic landmarks (Cross et al, 2000). Study of occurrence and characteristics of the CpG islands has gained great interests.…”

Section: Introductionmentioning

confidence: 99%

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The properties of CpG islands in the putative promoter regions of human immunoglobulin (Ig) genes

Liu

Zhang

Jiang

et al. 2005

Gene

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CpG is a GC rich motifs in the gene promoter region, which can play important roles in gene silencing and imprinting. This study examines the properties of CpG islands in the putative promoter regions have the CpG distributions in the two patterns. Moreover, the length of CpG islands is shorter in human Ig genes than in non-Ig genes, but much longer than in mouse orthologous. Thus, our data suggest that the occurrence and distribution of CpG islands in PPRs of human and mouse Ig genes is nonneutral and nonrandom, which may reflect the species and gene specification. Abstract:CpG is a GC rich motifs in the gene promoter region, which can play important roles in gene silencing and imprinting. This study examines the properties of CpG islands in the putative promoter regions (PPRs) of human and mouse immunoglobulin (Ig) genes. The in the two patterns. Moreover, the length of CpG islands is shorter in human Ig genes than in non-Ig genes, but much longer than in mouse orthologous. Thus, our data suggest that the occurrence and distribution of CpG islands in PPRs of human and mouse Ig genes is nonneutral and nonrandom, which may reflect the species and gene specification. Abstract 1The properties of CpG islands in the putative promoter regions of human immunoglobulin (Ig) genes

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CpG island libraries from human Chromosomes 18 and 22: landmarks for novel genes

Cited by 28 publications

References 3 publications

Functional Analysis of p53 Binding under Differential Stresses

Functional Analysis of p53 Binding under Differential Stresses

Identification of a novel gene, CDCP1, overexpressed in human colorectal cancer

The properties of CpG islands in the putative promoter regions of human immunoglobulin (Ig) genes

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