In mammals, it is crucial to express the right gene at the right time and in the right tissue; deregulation of this process leads to abnormal growth and development, like cancer. One of the important mechanisms by which mammals achieve such a regulation is by controlling transcription of RNA polymerase II genes through enhancers (long distance activation). However, our present knowledge of the principles, that regulate mammalian enhancer function, mainly stems from studies involving cell-free in vitro systems, or in vivo systems comprised of tissue culture cells or animal viruses. It has been relatively unknown how these principles apply under physiological conditions, for example, when a fertilized mammalian 1-cell embryo develops into an animal. This inability is primarily due to the limited availability of sufficient embryos to carry out biochemical studies. It is only recently that technologies have been developed allowing the study of gene expression in mammalian embryos as early as a fertilized 1-cell embryo, and in as few as a single embryo, using microinjection techniques. This provides an unprecedented opportunity to study these regulatory processes in the context of a living animal. The objective of this study is to utilize this opportunity to examine, on one hand, the general mechanism by which enhancers regulate gene expression during early mouse development, and on the other, the specific mechanism of action of a recently discovered long-distance repressor, that can potentially regulate neurogenesis by controlling a battery of neuron-specific genes. These experiments are expected to aid in the long term objective of understanding the overall regulation of transcription, by the interplay of long distance activation and long-distance repression, during mammalian embryonic development.
