Our laboratory studies how enhancers activate transcription during development and differentiation, with particular interest in the role played by chromatin structure in this process. The model system employed is the family of human globin genes that are expressed in a tissue-specific and developmentally regulated fashion under the influence of the β-globin locus control region enhancer (LCR). Studies are being carried out to map the precise changes in nucleosome organization that accompany gene activation and to understand the role of transcription factors and transcription and replication per se. Other studies using mutagenesis, and in vitro and in vivo ligation approaches, are addressing the extent to which the interaction of a promoter and an enhancer involves close contact. Another area of interest is in establishing which transcription factors and mediators are actually bound in vivo to a transcribing gene promoter or enhancer by using cross-linking and immunoprecipitation. The goal of these studies is to understand the complex interplay between nuclear genes and their modulators. Understanding the role of chromatin structure in gene regulation is important to gene therapy efforts.