Year 2

Less than 2% of the human genome encodes protein coding genes. But many trait specific and disease specific mutations seem to map away from such coding sequences. This paradox is partially resolved by observation that some of the noncoding sequences are involved in regulation of when and where in the developing organism genes are to be turned on and off. One class of such regulatory sequences is called enhancers, since they have a property to greatly enhance gene expression. During embryogenesis, enhancers are the most dynamically utilized part of the genome, but mechanisms dictating reorganization of enhancer patterns is response to changes in signaling environment are poorly understood. During this reporting period, we investigated molecular mechanisms that underlie selection of new enhancer regions for activation during transition between naïve and primed pluripotent states. We identified transcription factors that mediate opening up of the previously nucleosome-occluded regions, establishment of permissive enhancer chromatin states and changes in gene expression.