Abstract 5492: Comprehensive analysis of the dynamics of aberrant WNT signaling on global gene expression and nuclear structure

Abstract

Abstract The organization of the genome in the nucleus is complex and dynamic. Features of the nuclear architecture, including the spatial arrangement of genomic sequences, the structure of chromatin, and the accessibility of regulatory DNA elements modulate nuclear processes such as gene transcription DNA replication, DNA repair, RNA processing, and mRNA transport. However, the interplay between nuclear architecture and gene expression is poorly understood. We propose to elucidate the impact of silencing the prominent transcription factor, TCF7L2, the major effector of the WNT signaling pathway, on the transcriptional equilibrium and nuclear architecture of the nucleus in human colorectal cancer cells. Our multidisciplinary approach combines targeted silencing of TCF7L2, 3D-FISH, RNA-seq, and Hi-C chromosome conformation capture, in parallel with mathematical modeling to delineate structure/function relationships in the interphase nucleus. This approach will elucidate the intricacies of a dynamic cellular signaling pathway in three-dimensional space. Citation Format: Markus A. Brown. Comprehensive analysis of the dynamics of aberrant WNT signaling on global gene expression and nuclear structure [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5492. doi:10.1158/1538-7445.AM2017-5492