The pluripotency of the embryonic stem (ES) cells, i.e. the properties to proliferate indefinitely in culture and differentiate into virtually every other cell type in the body, is controlled by a handful of transcription factors, which are proteins that bind to DNA and selectively activate expression of specific genes. The main objective of this project is to understand how transcription factors mediate the selective activation of genes involved in pluripotency of the ES cells. In the current funding period, we have demonstrated that ES cell differentiation is accompanied by dynamic modifications of the histone proteins, the basic building blocks of the chromosomes that play critical roles in gene regulation. The dynamic histone modifications occur where these transcription factors bind, and appear to be both dependent on binding of the transcription factors, and capable of facilitating the their binding to the same regions. Thus, histone modifications and transcription factors together regulate the self-renewal and pluripotency of the ES cells.