HBB-LCR - beta-globin locus control region

This genomic sequence, which spans 34 kb upstream of the hemoglobin subunit epsilon 1 (HBE1) gene, represents the 5' regulatory region of the human beta-globin gene cluster on chromosome 11. It includes a locus control region (LCR), which can confer developmentally regulated, position-independent and copy number-dependent expression on linked beta-globin genes in transgenic mice. The LCR is the major element controlling expression of the downstream beta-globin genes (epsilon, G-gamma, A-gamma, delta and beta, or HBE1, HBG2, HBG1, HBD and HBB, respectively), which are organized on the chromosome in their order of developmental expression. This region includes several DNase I hypersensitive sites (HSs; 5'HS1-5'HS7 in the entire region, 5'HS1-5'HS5 in the LCR), some of which possess enhancer activity in erythroid cells and/or function in synergy (e.g., the 5'HS2 and 5'HS3 enhancers). The HSs bind to erythroid transcription factors and are associated with regulatory complexes involved in beta-globin gene expression and the organization of local chromatin domain structure. This region also includes matrix attachment regions (MARs), silencers, an enhancer-blocking element (at 5'HS5), a DNA-RNA triplex-forming region (at 5'HS2) that reduces beta-globin gene expression, and a retroviral element (ERV-9) with enhancer activity in erythrocytes. Chromosome conformation capture assays show that the LCR is an integral part of the beta-globin active chromatin hub in erythroid cells, where it undergoes looping interactions with distal 5' and 3' HSs (HS-111 and 3'HS1) and the active beta-globin gene promoters. A larger region that includes 5'HS2-5'HS5 of the LCR plus an additional 27 kb may regulate replication initiation at a replication origin (IR) in the vicinity of the adult beta-globin (HBB) gene. Mutations in this LCR result in beta-thalassemias and beta-hemoglobinopathies. A large naturally-occurring deletion, which includes the sequence spanning 5'HS2-5'HS7, results in Hispanic gamma-delta-beta thalassemia and a closed chromatin conformation across the beta-globin locus. [provided by RefSeq, Dec 2019]

NCBI Orthologs

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