@article {38582, title = {Derepression of Cancer/testis antigens in cancer is associated with distinct patterns of DNA hypomethylation}, journal = {BMC CancerBMC CancerBMC Cancer}, volume = {13}, year = {2013}, note = {Kim, Robert
Kulkarni, Prakash
Hannenhalli, Sridhar
eng
R01 GM100335/GM/NIGMS NIH HHS/
R01GM100335/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov{\textquoteright}t
England
2013/03/26 06:00
BMC Cancer. 2013 Mar 22;13:144. doi: 10.1186/1471-2407-13-144.}, pages = {144}, abstract = {BACKGROUND: The Cancer/Testis Antigens (CTAs) are a heterogeneous group of proteins whose expression is typically restricted to the testis. However, they are aberrantly expressed in most cancers that have been examined to date. Broadly speaking, the CTAs can be divided into two groups: the CTX antigens that are encoded by the X-linked genes and the non-X CT antigens that are encoded by the autosomes. Unlike the non-X CTAs, the CTX antigens form clusters of closely related gene families and their expression is frequently associated with advanced disease with poorer prognosis. Regardless however, the mechanism(s) underlying their selective derepression and stage-specific expression in cancer remain poorly understood, although promoter DNA demethylation is believed to be the major driver. METHODS: Here, we report a systematic analysis of DNA methylation profiling data from various tissue types to elucidate the mechanism underlying the derepression of the CTAs in cancer. We analyzed the methylation profiles of 501 samples including sperm, several cancer types, and their corresponding normal somatic tissue types. RESULTS: We found strong evidence for specific DNA hypomethylation of CTA promoters in the testis and cancer cells but not in their normal somatic counterparts. We also found that hypomethylation was clustered on the genome into domains that coincided with nuclear lamina-associated domains (LADs) and that these regions appeared to be insulated by CTCF sites. Interestingly, we did not observe any significant differences in the hypomethylation pattern between the CTAs without CpG islands and the CTAs with CpG islands in the proximal promoter. CONCLUSION: Our results corroborate that widespread DNA hypomethylation appears to be the driver in the derepression of CTA expression in cancer and furthermore, demonstrate that these hypomethylated domains are associated with the nuclear lamina-associated domains (LADS). Taken together, our results suggest that wide-spread methylation changes in cancer are linked to derepression of germ-line-specific genes that is orchestrated by the three dimensional organization of the cancer genome.}, keywords = {*DNA Methylation, *Gene Expression Regulation, Neoplastic, *Genes, X-Linked, Antigens, Neoplasm/*genetics, Binding Sites, Cluster Analysis, CpG Islands, Gene Expression Profiling, HUMANS, Male, Neoplasms/*genetics/*metabolism, Promoter Regions, Genetic, Protein Binding, Protein Interaction Domains and Motifs, Testis/*metabolism}, isbn = {1471-2407 (Electronic)
1471-2407 (Linking)}, author = {Kim, R. and Kulkarni, P. and Sridhar Hannenhalli} } @article {49681, title = {Spliceosomal small nuclear RNA genes in 11 insect genomes.}, journal = {RNA}, volume = {13}, year = {2007}, month = {2007 Jan}, pages = {5-14}, abstract = {

The removal of introns from the primary transcripts of protein-coding genes is accomplished by the spliceosome, a large macromolecular complex of which small nuclear RNAs (snRNAs) are crucial components. Following the recent sequencing of the honeybee (Apis mellifera) genome, we used various computational methods, ranging from sequence similarity search to RNA secondary structure prediction, to search for putative snRNA genes (including their promoters) and to examine their pattern of conservation among 11 available insect genomes (A. mellifera, Tribolium castaneum, Bombyx mori, Anopheles gambiae, Aedes aegypti, and six Drosophila species). We identified candidates for all nine spliceosomal snRNA genes in all the analyzed genomes. All the species contain a similar number of snRNA genes, with the exception of A. aegypti, whose genome contains more U1, U2, and U5 genes, and A. mellifera, whose genome contains fewer U2 and U5 genes. We found that snRNA genes are generally more closely related to homologs within the same genus than to those in other genera. Promoter regions for all spliceosomal snRNA genes within each insect species share similar sequence motifs that are likely to correspond to the PSEA (proximal sequence element A), the binding site for snRNA activating protein complex, but these promoter elements vary in sequence among the five insect families surveyed here. In contrast to the other insect species investigated, Dipteran genomes are characterized by a rapid evolution (or loss) of components of the U12 spliceosome and a striking loss of U12-type introns.

}, keywords = {Animals, Base Sequence, Bees, Computational Biology, Diptera, Evolution, Molecular, Genes, Insect, Genome, Insect, Molecular Sequence Data, Nucleic Acid Conformation, Phylogeny, Promoter Regions, Genetic, RNA Splicing, RNA, Small Nuclear, Sequence Analysis, RNA, Spliceosomes}, issn = {1355-8382}, doi = {10.1261/rna.259207}, author = {Mount, Stephen M and Gotea, Valer and Lin, Chiao-Feng and Hernandez, Kristina and Makalowski, Wojciech} }