Identification of Y-Box Binding Protein 1 As a Core Regulator of MEK/ERK Pathway-Dependent Gene Signatures in Colorectal Cancer Cells

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties

Mapping of easy to screen SSR markers for selection of RFLP markers-bracketed downy mildew resistance QTLs in pearl millet

Pearl millet (Pennisetum glaucum L.), the sixth most important food-grain crop, is a highly nutritious and multipurpose cereal which can grow in the poorest soil. The crop suffers from substantial annual yield losses due to devastating downy mildew (DM) disease caused by fungus Sclerospora graminicola. Using a F2 population derived from the cross of H 77/833-2 and ICMP 451, linkage groups 1 and 4 have been reported to carry QTLs for resistance to Sclerospora graminicola. These QTLs were bracketed with labour intensive restriction fragment length polymorphism markers thus hampering their use in marker assisted selection (MAS). The current study reports saturation of DM resistance QTL regions with easy to screen simple sequence repeats markers which can be efficiently utilized in MAS programmes for improving the elite cultivars of pearl millet against this disease.Peer reviewe