Analysis of Epigenetic Dysregulation Mediated by LLPS in Cancers

Epigenetic gene regulatory mechanisms play a central role in the biological control of cell and tissue structure, function and phenotype. Much of the research in the field of cancer has focused on the determinants of genetic alterations that inhibit or promote the acquisition of the cancer phenotype. Liquid-liquid phase separation (LLPS) is involved in regulating different epigenetic stages, including transcription, chromatin organization, 3D DNA structure, splicing and post-transcriptional modifications, and plays an important role in cancer development, progression and metastasis. In addition, some membrane-free organelles formed through LLPS are also involved in epigenetic regulation, and their defects are associated with cancer development.

Fig. 1. Interaction between pseudogenes and LLPS to mediate cancer. (Nsengimana B, et al., 2022)

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LLPS affects different levels of epigenetic expression. Our study focuses on the dysregulation of several variables of epigenetic expression leading to cancer formation. CD BioSciences offers specialized services to analyze the different stages of epigenetic expression affected by LLPS, including chromatin organization, transcriptional regulation, RNA splicing, non-coding RNA metabolism and poly N6-adenine methylation (m⁶A) modifications.

• Analysis of LLPS Dysregulation in Chromatin Organization
  A high frequency of mutations in genes encoding elements that regulate chromatin structure has been identified in many cancers, including genetic alterations that regulate the phase-separated droplet components of chromatin organization. We provide in vitro and in vivo experiments to characterize LLPS-mediated reorganization of chromatin topology in condensates, containing EBNA2, BAF complexes, and EWSR1, etc.
• Analysis of LLPS Dysregulation in Non-Coding RNA
  Pseudogenes are considered to be non-functional relatives of genes that have lost their protein-coding ability. Pseudogenes can affect the LLPS process. We can analyze the relationship between aberrant pseudogene expression (e.g. Long Interspersed Element-1) and LLPS formation with cancer, and further develop pseudogenes as biomarkers for cancer diagnosis.
• Analysis of LLPS Dysregulation in m⁶A Modifications
  m⁶A is the most prevalent mRNA modification. We can analyze the role of m⁶A in LLPS and gene expression control by characterizing the phase separation concentrates of m⁶A-enhancer RNA and YTHDC1. In addition, we are developing a model of the relationship between LLPS dysregulation and cancer due to defective m⁶A expression. Our technical team is continuing to explore the impact of other RNA modifications on LLPS formation.

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

• BRD4
• HP1a  
• m⁶A
• Polycomb
• MeCP2 (Breast cancer)
• MALAT1
• ASXL1 (Myeloid tumor)

Combining proteomics, transcriptomics, imaging, genetics, epidemiology and computer data, CD BioSciences aims to analyze the different stages of epigenetic expression affected by LLPS, to help our clients develop promising 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.