Developmental regulation of the vertebrate globin multigene family.

"Hemoglobin switching," or the sequential expression of globin genes in erythroid cells during development, has provided an important paradigm for tissue- and stage-specific gene regulation. Over the past decade, regulatory DNA sequences and transcription factors involved in controlling the expression of individual globin genes in erythroid cells have been identified. The picture that has emerged indicates that gene proximal control elements collaborate with a "locus control region" located far upstream - probably via a DNA looping mechanism - to ensure that each gene is turned on only in erythroid cells and at the appropriate time during development. Interactions among the various regulatory sequences are thought to be mediated and stabilized by an array of tissue-specific and ubiquitous proteins. Chromatin structure plays a critical but still poorly understood role in this process.