Further understanding of the beta-globin locus regulation at the molecular level: looping or linking models?

The human beta-globin locus is a classic model of the eukaryotic multigene family with tissue- and temporally specific expression. Over the past few years, great advances have been achieved in studies of beta-globin locus regulation. The dominant role of the beta-globin locus control region (LCR) in chromatin opening and developmental switching has been challenged, and elements beyond the LCR have been studied in depth. More recently, the fields of research have been expanded to intergenic transcription, nuclear localization and histone modification. Several models have been proposed to elucidate the regulation mechanism; among them, the looping and linking models are the most prevalent. Different models are the summarization of the observations made at different times and a persuasive model must be based on a systematic understanding of the numerous observations. The objective of this review is to provide an overview of progress in the area of beta-globin regulation and then to discuss models for it.