Chromatin Assembly: Role of chromodomain protein CHD1

Within the eukaryotic nucleus, DNA and the conserved histone proteins form a highly ordered structure termed chromatin. The assembly of DNA into chromatin is a fundamentally important process that is required for the duplication of chromosomes during cell growth. In addition, chromatin structure must be taken apart and reassembled during DNA repair and transcription. Thus, chromatin assembly interfaces many important nuclear processes. Assembly and remodelling of chromatin play critical roles in the regulation of the activity state of the genome which in some instances can be inherited by subsequent generations. These processes are therefore counted among the epigenetic mechanisms of gene regulation.The long-term interest of our research is to understand the mechanisms and factors that act to assemble and modulate chromatin structure and thereby affect processes of DNA metabolism, in particular transcription. In this project, we have focused our studies on the functions of the chromatin assembly factor CHD1, and we have used the fruit fly as a genetic model organism. One of the major findings of these studies was that CHD1 is a crucial factor during the process of fertilization. It enables the sperm nucleus to fuse with the nucleus of the egg cell by globally reorganizing the sperm chromatin. In the absence of CHD1, this fusion cannot take place and embryonic development is aborted. Moreover, we have investigated which parts of the CHD1 protein are important for its functions, and we found that CHD1 is necessary for transcription during stress conditions, such as heat shock. We also discovered that, in the fly, CHD1 is important for maintaining a proper balance of the microbiota of the gut. If CHD1 is deleted, gut bacteria overgrow and the flies are more susceptible to food-borne bacterial infections. These and further results underline the profound effects on the life of an organism that are brought about by the remodelling of chromatin structure, and they highlight the potential of the components of epigenetic processes as targets for the diagnosis and treatment of human disease.