Research Projects

Chromatinopathy is a genetic disorder resulting from errors in chromatin organization and transcription regulation. These can be caused by mutations in proteins like CTCF and cohesin, transcription factors, or epigenetic modulators. They can cause developmental delays, growth retardation, intellectual disability, and behavioral disturbances. Cornelia de Lange Syndrome (CdLS) is a classic example of chromatinopathy, a genetic disorder characterized by developmental delay, growth retardation, intellectual disability, and behavioral disturbances. Cohesin, a ring-shaped protein, plays a crucial role in sister chromatid cohesion, DNA replication, cell division, DNA repair, and genomic stability. Recently, NGS-based chromatin conformation capture and high-resolution imaging techniques have allowed for the formation of Topologically Associating Domains (TADs), functional units of three-dimensional chromatin organization. TADs restrict the action of regulatory elements to genes within them. Deregulation of TADs can rewire contacts between regulatory elements and target genes, leading to altered gene expression. The impact of mutations in cohesin on chromatin organization has not been fully explored due to its recent discovery and limited technical expertise. This study aims to fill this gap by introducing mutations in mouse embryonic stem cells, which will be differentiated into neural precursors and neuronal cells. The study will explore how mutations impact global binding of proteins to DNA, accessibility of chromatin to other transcription factors, organization of chromatin in three-dimensional space, and gene expression. The findings could aid in patient classification, risk prediction, treatment choice, and the development of novel therapeutic agents.