Visualisation of chromatin dynamics during early mammalian embryogenesis – VisualChromatin
Genomic reprogramming reverts fully differentiated cells to toti- or pluripotent state to start a new developmental program. In the early mouse embryo, fully differentiated gametes are reprogrammed after fertilization to totipotent- and subsequently to the pluripotent state. Epigenetic reprogramming is accompanied by drastic changes in the pattern of gene expression. Nuclear architecture has recently emerged as a key-factor in the regulation of gene expression. Although the nuclear organization is also restructured during early development, how nuclear architecture influences essential developmental processes still remains largely unknown. Here, we will decipher the role of nuclear architecture in two key processes ocurring in early development: lineage choice determination and X-chromosome inactivation. First, to clarify the behavior of global chromosomal organization in the early embryo, we propose to map chromosomal territories in several stages of early embryonic development. Second, to specify the interrelation between nuclear architecture we will visualise the dynamics of key loci known for their epigenetic changes in development (Nanog and Cdx2 on the one hand, and X-chromosome linked loci on the other) during early embryogenesis using a 4D live cell imaging system for tracing specific gene loci. With this system, we will observe the dynamic behavior of gene loci and gene expression throughout development. Third, we will follow the chromatin dynamics of these loci in respect to different nuclear compartments during ealry embryogenesis as well as their positioning within euchromatin and heterochromatin. Finally, through the analysis of incorporation of tagged histone variants we will define the contribution of each of these variants to nuclear organisation of these loci. Taking these analyses together, the results from this project will establish the role of nuclear architecture in cell fate decisions and X-chomosome inactivation. This project will give us important insights into epigenetic reprogramming, early mammalian development and stem cell biology.
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