Amin, R. — Page 2 | bioRxiv Science

bioRxiv2020

Targeting nuclear pore protein, NUP210, reduces metastasis through heterochromatin-mediated silencing of mechanosensitive genes

Mechanical signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identified nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor positive (ER+) breast cancer and a cellular mechanosensor. Nup210 depletion suppresses lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with LINC complex protein SUN2 which connects the nucleus to the cytoskeleton. In addition, the NUP210/SUN2 complex interacts with chromatin via the short isoform of BRD4 and histone H3.1/H3.2 at the nuclear periphery. In Nup210 knockout cells, mechanosensitive genes accumulate H3K27me3 heterochromatin modification, mediated by the polycomb repressive complex 2 and differentially reposition within the nucleus. Transcriptional repression in Nup210 knockout cells results in defective mechanotransduction and focal adhesion necessary for their metastatic capacity. Our study provides a new insight into the role of nuclear pore protein in cellular mechanosensation and metastasis.

cancer biology↗

bioRxiv2019

iPromoter-BnCNN: a Novel Branched CNN Based Predictor for Identifying and Classifying Sigma Promoters

MotivationPromoter is a short region of DNA which is responsible for initiating transcription of specific genes. Development of computational tools for automatic identification of promoters is in high demand. According to the difference of functions, promoters can be of different types. Promoters may have both intra and inter class variation and similarity in terms of consensus sequences. Accurate classification of various types of sigma promoters still remains a challenge. ResultsWe present iPromoter-BnCNN for identification and accurate classification of six types of promoters -{sigma} 24,{sigma} 28,{sigma} 32,{sigma} 38,{sigma} 54,{sigma} 70. It is a CNN based classifier which combines local features related to monomer nucleotide sequence, trimer nucleotide sequence, dimer structural properties and trimer structural properties through the use of parallel branching. We conducted experiments on a benchmark dataset and compared with six state-of-the-art tools to show our supremacy on 5-fold cross-validation. Moreover, we tested our classifier on an independent test dataset. AvailabilityOur proposed tool iPromoter-BnCNN web server is freely available at http://103.109.52.8/iPromoter-BnCNN. The runnable source code can be found here. Contactrafeed@cse.uiu.ac.bd Supplementary informationSupplementary data (benchmark dataset, independent test dataset, model files, structural property information, attention mechanism details and web server usage) are available at Bioinformatics. online.

genomics↗