Anaswara Vijayakumar

Moldova

Single-Cell Resolution Mapping of Non-Coding Regulatory Elements Using ENCODE Data: Avenues to Therapeutic Targets for Precision Medicine

Kuzhipurayidathil Vijayakumar Anaswara1,Anand Muraleedharan1,Daria Zalesskaia1,Fauizi Mohammad1, Ludmila Sidorenko1,2
1. Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova
2.Department of molecular biology and genetics, Chisinau, Moldova

Abstract

Background

Non-coding regulatory elements (NCREs), such as enhancers and promoters, coordinate gene expression and perform a vital function in cell-type-specific functions. Advances in genomic technologies and comprehensive datasets such as those provided by the ENCODE Project have enabled very detailed mapping of NCREs. With single-cell technologies emerging, it becomes possible to devise a framework for defining NCRE activity in unparalleled resolution, keeping the path open to targeted therapeutic interventions for specific cellular contexts.

Methods

The bibliographic sources included in the study were based on online resources published between 2014 and 2024, including PubMed, Google Scholar, Science Direct, Nature Journals and others.

Results

Combining single-cell transcriptomic data and chromatin accessibility data from the ENCODE project, the researchers managed to develop high-resolution atlas for the mapping of NCREs. They found that there are new over 50,000 regulatory elements that have not been annotated by previous methods, many of which show evidence of histone modification, such as H3K27ac and H3K4me1, pointing towards an active regulatory function. Integration with genome-wide association studies: GWAS showed that many of the associated disease-related single nucleotide polymorphisms did lie within these NCREs. For example, in Alzheimer’s disease, the SNPs within the microglial enhancer regions correlated with an aberrant expression of the genes TREM2 and APOE. Functional validation in cell models relevant to the diseases shows that these NCREs modulate gene expression and phenotypic outcomes, thus indicating great potential for therapeutic interventions.

Conclusions

This study highlights how it can be used to investigate the regulatory landscape of human cells in great detail using a combination of ENCODE data and single-cell technologies. The study advances knowledge on cell type-specific gene regulation while providing a basis to identify and target NCREs in precise medicine. These insights can also be used to formulate cell-specific therapeutic approaches for diseases associated with the aberrant expression of genes.