Analysis of Transcriptional Regulation Mediated by LLPS in Cancers

Cell type-specific transcriptional programs are regulated by enhancers that are remote from these genes. Super enhancers play a multifaceted role in disease biology. For example, super-enhancers are found in cancer cells often generated near various oncogenes and other genes important for various aspects of cancer biology. Based on the multi-layered cooperation between interacting factors and multiple superenhancer components, scientists have proposed the formation of biomolecular condensates as the working principle of superenhancers. Several terms, including "transcription factories", "transcriptional condensates", "transcriptional hubs", and "MegaTrans complexes" have been used to describe such transcription-related multimolecular assemblies. This condensates model includes the observation of large clusters of RNA Pol II in live mammalian cells by super-resolution imaging to explain the hyper-sensitivity of super-enhancers to transcriptional perturbations.

Fig. 1. Enhanced phase-separation by transcription factor collaborations for prostate cancer progression. (Takayama KI, et al., 2022)

Customized Services

Transcriptional dysregulation is a key feature of cancer, and genetic alterations regulating the liquid-liquid phase separation (LLPS) droplet component of chromatin organization have been found in many cancers. Our experts attempt to explain transcriptional bursts using LLPS. CD BioSciences offers specialized services to analyze LLPS-mediated chromatin regulation in cancers.

In collaboration with cancer researchers, cell biologists and biophysicists, we offer cutting-edge technologies to analyze transcriptional condensates in cancers, as shown below. If you would like to analyze transcriptional condensates in other cancers, you can contact us directly for a customized service.

• FET fusion (Ewing sarcoma)
• NUP98 fusion (Ewing sarcoma)
• YAP, TAZ (Breast cancer)
• AKAP95 (Breast cancer)
• OCT4 (Breast cancer)
• SRC1 (Lung cancer)
• HOXB8/FOSL1/AP-1 complex (Osteosarcoma)
• SRC-3, NSD2 (Myeloma)
• SPOP (Stomach cancer, liver cancer and prostate cancer)

Critical transcription factors (TF) undergo LLPS in super-enhancers and play a key role in the epigenetic and genetic regulation of cancer progression. Our lab has a sophisticated cellular, in vivo, computer, and bioinformatics one-stop platform to help our clients analyze the mechanisms linking the potential transcriptional activation of TF via LLPS to cancer development. Intriguingly, our technical team develop the use of TF-mediated phase separation as an effective therapeutic strategy for the treatment of drug-resistant cancers.

• Small molecule cancer therapeutic strategies that target transcriptional condensates.
• Cancer drug design that directly targets transcriptional condensate kinetics.

Combining proteomics, transcriptomics, imaging, genetics, epidemiology and computer data, CD BioSciences aims to analyze the relationship between super enhancers and biomolecular condensates models, and the phase transition of transcriptional condensates in cancer, to help our clients develop therapeutic targets for cancer treatment. Our services are widely used in preclinical research in cancer biology, diagnosis and treatment. If you are interested in our services, please feel free to contact us.