HBB-LCR beta-globin locus control region [Homo sapiens (human)] - Gene

Summary

Gene symbol: HBB-LCR
Gene description: beta-globin locus control region
Primary source: MIM:152424
Gene type: biological region
Feature type(s): misc_structure
mobile_element
protein_bind
regulatory: CAAT_signal, DNase_I_hypersensitive_site, TATA_box, enhancer, enhancer_blocking_element, insulator, locus_control_region, matrix_attachment_region, promoter, silencer, transcriptional_cis_regulatory_region
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LCRB; LCR-beta; beta-DCR; beta-LAR
Summary: 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]
Orthologs: mouse all
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Genomic context

Location:: 11p15.4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (5269925..5304186)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (5329290..5363538)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (5291155..5325416)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Structural switching/polymorphism by sequential base substitution at quasi-palindromic SNP site (G --> A) in LCR of human beta-globin gene cluster.
Title: Structural switching/polymorphism by sequential base substitution at quasi-palindromic SNP site (G → A) in LCR of human β-globin gene cluster.
Autonomous silencing is the main mechanism controlling gamma-gene expression in the adult.
Title: Autonomous silencing as well as competition controls gamma-globin gene expression during development.

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Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
beta Thalassemia MedGen: C0005283 GeneReviews: Beta-Thalassemia	Compare labs
Beta-thalassemia HBB/LCRB MedGen: CN322236 OMIM: 613985 GeneReviews: Beta-Thalassemia	Compare labs

Variation

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See variants in ClinVar

See Variation Viewer (GRCh37.p13)

General gene information

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Other Names

CRISPR perturbation-validated HBE1, HBG1, HBG2, HBBP1, HBD and HBB cis-regulatory elements
beta Glb-LCR
beta-globin 5' regulatory region
beta-globin LCR
beta-globin dominant control region
beta-globin locus activation region
beta-globin locus-activating region
locus control region, beta

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.