Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by M. Costa
Total Records ( 2 ) for M. Costa
  Q Li , Q Ke and M. Costa
 

In the present study, we examined the effects of CoCl2 on multiple histone modifications at the global level. We found that in both human lung carcinoma A549 cells and human bronchial epithelial Beas-2B cells, exposure to CoCl2 (≥200 µM) for 24 h increased H3K4me3, H3K9me2, H3K9me3, H3K27me3, H3K36me3, uH2A and uH2B but decreased acetylation at histone H4 (AcH4). Further investigation demonstrated that in A549 cells, the increase in H3K4me3 and H3K27me3 by cobalt ions exposure was probably through enhancing histone methylation processes, as methionine-deficient medium blocked the induction of H3K4me3 and H3K27me3 by cobalt ions, whereas cobalt ions increased H3K9me3 and H3K36me3 by directly inhibiting JMJD2A demethylase activity in vitro, which was probably due to the competition of cobalt ions with iron for binding to the active site of JMJD2A. Furthermore, in vitro ubiquitination and deubiquitination assays revealed that the cobalt-induced histone H2A and H2B ubiquitination is the result of inhibition of deubiquitinating enzyme activity. Microarray data showed that exposed to 200 µM of CoCl2 for 24 h, A549 cells not only increased but also decreased expression of hundreds of genes involved in different cellular functions, including tumorigenesis. This study is the first to demonstrate that cobalt ions altered epigenetic homeostasis in cells. It also sheds light on the possible mechanisms involved in cobalt-induced alteration of histone modifications, which may lead to altered programs of gene expression and carcinogenesis since cobalt at higher concentrations is a known carcinogen.

  H Chen , T Kluz , R Zhang and M. Costa
 

Epigenetic silencing of tumor suppressor genes commonly occurs in human cancers via increasing DNA methylation and repressive histone modifications at gene promoters. However, little is known about how pathogenic environmental factors contribute to cancer development by affecting epigenetic regulatory mechanisms. Previously, we reported that both hypoxia and nickel (an environmental carcinogen) increased global histone H3 lysine 9 methylation in cells through inhibiting a novel class of iron- and -ketoglutarate-dependent histone demethylases. Here, we investigated whether inhibition of histone demethylase JMJD1A by hypoxia and nickel could lead to repression/silencing of JMJD1A-targeted gene(s). By using Affymetrix GeneChip and ChIP-on-chip technologies, we identified Spry2 gene, a key regulator of receptor tyrosine kinase/extracellular signal-regulated kinase (ERK) signaling, as one of the JMJD1A-targeted genes in human bronchial epithelial BEAS-2B cells. Both hypoxia and nickel exposure increased the level of H3K9me2 at the Spry2 promoter by inhibiting JMJD1A, which probably led to a decreased expression of Spry2 in BEAS-2B cells. Repression of Spry2 potentiated the nickel-induced ERK phosphorylation, and forced expression of Spry2 in BEAS-2B cells decreased the nickel-induced ERK phosphorylation and significantly suppressed nickel-induced anchorage-independent growth. Taken together, our results suggest that histone demethylases could be targets of environmental carcinogens and their inhibition may lead to altered gene expression and eventually carcinogenesis.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility