SUMMARY Many essential cellular processes, such as gene control, employ elaborate mechanisms involving the coordination of large, multi-component molecular assemblies. Few structural biology tools presently have the combined spatial-temporal resolution and molecular specificity required to capture the movement, conformational changes, and sub-unit association-dissociation kinetics, three fundamental elements of how such intricate molecular machines work. Here, we report a 3D single-molecule super-resolution imaging study using modulation interferometry and phase-sensitive detection that achieves <2 nm axial localization precision, well below the few-nanometer-sized individual protein components. To illustrate the capability of this technique in probing the dynamics of complex macromolecular machines, we visualize the movement of individual multi-subunit E. coli RNA polymerases through the complete transcription cycle, dissect the kinetics of the initiation-elongation transition, and determine the fate of σ70 initiation factors during promoter escape. Modulation interferometry sets the stage for single-molecule studies of several hitherto difficult-to-investigate multi-molecular transactions that underlie genome regulation.

Dysregulation of gene expression plays an important role in cancer development. Identifying transcriptional regulators, including transcription factors and chromatin regulators, that drive the oncogenic gene expression program is a critical task in cancer research. Genomic profiles of active transcriptional regulators from primary cancer samples are limited in the public domain. Here we present BART Cancer (bartcancer.org), an interactive web resource database to display the putative transcriptional regulators that are responsible for differentially regulated genes in 15 different cancer types in The Cancer Genome Atlas (TCGA). BART Cancer integrates over 10000 gene expression profiling RNA-seq datasets from TCGA with over 7000 ChIP-seq datasets from the Cistrome Data Browser database and the Gene Expression Omnibus (GEO). BART Cancer uses Binding Analysis for Regulation of Transcription (BART) for predicting the transcriptional regulators from the differentially expressed genes in cancer samples compared to normal samples. BART Cancer also displays the activities of over 900 transcriptional regulators across cancer types, by integrating computational prediction results from BART and the Cistrome Cancer database. Focusing on transcriptional regulator activities in human cancers, BART Cancer can provide unique insights into epigenetics and transcriptional regulation in cancer, and is a useful data resource for genomics and cancer research communities.

lack of mechanistic insight is due, in part, to an oversimplification of the disease process as a static end state (e.g. ''hypertrophy vs dilation''), where it is now clear that cardiac remodeling in sarcomeric cardiomyopathies is a complex, progressive process that includes an early ''preclinical'' stage prior to overt disease. It is this preclinical stage that defines or represents the biophysical basis of sarcomeric cardiomyopathies and where approaches to alter the natural history of this disorder are focusing. Developing these novel therapeutic approaches will require understanding of atom-level changes in sarcomeric dynamics coupled to precise in vitro methods to measure sarcomeric performance in biologically relevant complexes and, importantly, coherent animal models with which to study the progressive outcomes of molecular interventions at the whole organ level. In this talk the development and application of our integrative in silico-in vitro-in vivo approach to real-world clinical questions will be explored.

Dysregulation of gene expression plays an important role in cancer development. Identifying transcriptional regulators, including transcription factors and chromatin regulators, that drive the oncogenic gene expression program is a critical task in cancer research. Genomic profiles of active transcriptional regulators from primary cancer samples are limited in the public domain. Here we present BART Cancer (bartcancer.org), an interactive web resource database to display the putative transcriptional regulators that are responsible for differentially regulated genes in 15 different cancer types in The Cancer Genome Atlas (TCGA). BART Cancer integrates over 10,000 gene expression profiling RNA-seq datasets from TCGA with over 7,000 ChIP-seq datasets from the Cistrome Data Browser database and the Gene Expression Omnibus (GEO). BART Cancer uses Binding Analysis for Regulation of Transcription (BART) for predicting the transcriptional regulators from the differentially expressed genes in cancer samples compared to normal samples. BART Cancer also displays the activities of over 900 transcriptional regulators across cancer types, by integrating computational prediction results from BART and the Cistrome Cancer database. Focusing on transcriptional regulator activities in human cancers, BART Cancer can provide unique insights into epigenetics and transcriptional regulation in cancer, and is a useful data resource for genomics and cancer research communities.

The goal of this study is to develop a comprehensive data resource for transcriptional regulator activities in various cancers. Dysregulation of gene expression plays an important role in cancer development. Identifying transcriptional regulators (TRs), including transcription factors and chromatin regulators, that drive the oncogenic gene expression program is a critical task in cancer research. Genomic TR profiling data from primary cancer samples are limited in the public domain. Here, we present BART Cancer, an interactive web resource database to display putative TRs that are responsible for regulating differentially expressed genes across 15 different cancer types included in The Cancer Genome Atlas (TCGA). BART Cancer integrates over 10,000 gene expression profiling RNA-seq datasets from TCGA with over 7,000 ChIP-seq datasets from the Cistrome Data Browser database and the Gene Expression Omnibus (GEO). BART Cancer uses Binding Analysis for Regulation of Transcription (BART) for predicting TRs from differentially expressed genes comparing cancer samples with normal samples for each cancer type. BART Cancer also displays the activities of over 900 TRs across cancer types, by integrating computational prediction results from BART and from the Cistrome Cancer database. Focusing on transcriptiona regulatory activities in human cancers, BART Cancer provides unique insights into epigenetics and transcriptional regulation in cancer, and is a useful data resource for genomics and cancer research communities. BART Cancer web resource can be accessed at: http://bartcancer.org. Citation Format: Zachary V. Thomas, Zhenjia Wang, Chongzhi Zang. BART cancer: A web resource for transcriptional regulators in cancer genomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 213.