Abstract Chromatin structure plays a critical role in eukaryotic gene transcriptional regulation. The β-globin locus provides an ideal system within which to study the interplay between chromatin structure and transcriptional regulation. The process of β-globin locus activation is remarkably intricate and involves at least two distinct events: chromatin opening and gene activation. Great progress has been made in recent years in understanding how locus control regions confer high-level expression to linked genes. Current interest focuses on some special events, including formation of locus control region hypersensitivity sites, ATP-dependent chromatin remodeling, localized H3 hyperacetylation, and intergenic transcription, which link chromatin and β-globin locus regulation. These events, and their possible molecular bases, are summarized together with speculations concerning their connections.