Signaling and Chromatin Dynamics during cell development, differentiation, and disease
In metazoans, the discovery of cell type-specific, a non-random higher-order organization of chromatin and long-range intra- and interchromosomal interactions between genes and their regulatory element, point to the functional interplay between 3-Dimensional genome architecture and gene expression. Recent data suggest that active and repressed genes from different chromosomal regions spatially constrain and functionally organize in conjunction with RNA Pol II-enriched transcription factories or Polycomb group (PcG) enriched silencing factories respectively. Moreover, the chromatin architectural protein CTCF or/and cohesion mediates long-range chromatin interactions and are thought to bring distant chromatin elements to the sites of ongoing transcription. However, the causal relationships between genome architecture and gene expression in the context of various nuclear subdomains and epigenetic features at a genome-wide scale are yet to be determined. In this regard, we are interested to study the mechanism behind global interphase chromosomal positioning and its influence on the orchestration of preferential physical gene networks within the cell nucleus and their dynamic changes during the course of cellular development, differentiation and disease. In this study we use high-throughput genomic technologies, such as Chromosome Conformation Capture (3C) and related methods, utilizing a wide variety of genetic and cell line model systems (Embryonic stem cell differentiation, Differentiation of T-Lymphocyte sub-types) in combination with bioinformatics and other computational approaches. We anticipate that system-level understanding of the physical and functional organization of chromatin in the cell nucleus and its relation to various nuclear domains and epigenetic features are essential to our understanding of governing principles in the orchestration of cell type-specific gene expression programming.