The human β-globin locus is composed of five

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s located on a short region of

chromosome 11 Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...

, responsible for the creation of the beta parts (roughly half) of the oxygen transport protein

Haemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...

. This locus contains not only the beta globin gene but also

delta Delta commonly refers to: * Delta (letter) (Δ or δ), a letter of the Greek alphabet * River delta, at a river mouth * D ( NATO phonetic alphabet: "Delta") * Delta Air Lines, US * Delta variant of SARS-CoV-2 that causes COVID-19 Delta may also ...

, gamma-A, gamma-G, and

epsilon Epsilon (, ; uppercase , lowercase or lunate ; el, έψιλον) is the fifth letter of the Greek alphabet, corresponding phonetically to a mid front unrounded vowel or . In the system of Greek numerals it also has the value five. It was der ...

globin. Expression of all of these genes is controlled by single locus control region (LCR), and the genes are differentially expressed throughout development. The order of the genes in the beta-globin cluster is: 5' -

– gamma-G – gamma-A –

–

beta Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labiod ...

- 3'. The arrangement of the genes directly reflects the temporal differentiation of their expression during development, with the early-embryonic stage version of the gene located closest to the LCR. If the genes are rearranged, the gene products are expressed at improper stages of development. Expression of these genes is regulated in embryonic

erythropoiesis Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. It is stimulated by decrea ...

by many

transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The func ...

, including KLF1, which is associated with the upregulation of adult hemoglobin in adult definitive

erythrocytes Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

, and

KLF2 Krüppel-like Factor 2 (KLF2), also known as lung Krüppel-like Factor (LKLF), is a protein that in humans is encoded by the ''KLF2'' gene on chromosome 19. It is in the Krüppel-like factor family of zinc finger transcription factors, and it has ...

, which is vital to the expression of

embryonic hemoglobin The human embryonic haemoglobins were discovered in 1961. These include Hb-Gower 1, consisting of 2 zeta chains and 2 epsilon chains, and Hb-Gower 2, which consists of 2 αlpha-chains and 2 epsilon-chains, the zeta and epsilon chains being the embr ...

HBB complex

Many CRMs have been mapped within the cluster of genes encoding β-like globins expressed in embryonic (HBE1), fetal (HBG1 and HBG2), and adult (HBB and HBD) erythroid cells. All are marked by

DNase I hypersensitive site In genetics, DNase I hypersensitive sites (DHSs) are regions of chromatin that are sensitive to cleavage by the DNase I enzyme. In these specific regions of the genome, chromatin has lost its condensed structure, exposing the DNA and making it acc ...

s and

footprint Footprints are the impressions or images left behind by a person walking or running. Hoofprints and pawprints are those left by animals with hooves or paws rather than feet, while "shoeprints" is the specific term for prints made by shoes. The ...

s, and many are bound by

GATA1 GATA-binding factor 1 or GATA-1 (also termed Erythroid transcription factor) is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by ...

peripheral blood derived erythroblast A peripheral or peripheral device is an auxiliary device used to put information into and get information out of a computer. The term ''peripheral device'' refers to all hardware components that are attached to a computer and are controlled by th ...

s (PBDEs). A DNA segment located between the HBG1 and HBD genes is one of the DNA segments bound by

BCL11A B-cell lymphoma/leukemia 11A is a protein that in humans is encoded by the ''BCL11A'' gene. Function The ''BCL11A'' gene encodes for a regulatory C2H2 type zinc-finger protein, that can bind to the DNA. Five alternatively spliced transcript va ...

and several other proteins to negatively regulate HBG1 and HBG2. It is sensitive to

DNase I Deoxyribonuclease I (usually called DNase I), is an endonuclease of the DNase family coded by the human gene DNASE1. DNase I is a nuclease that cleaves DNA preferentially at phosphodiester linkages adjacent to a pyrimidine nucleotide, yielding ...

but is not conserved across

mammals Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

. An enhancer located 3′ of the HBG1 gene is bound by several proteins in PBDEs and

K562 cell K562 cells were the first human immortalised myelogenous leukemia cell line to be established. K562 cells are of the erythroleukemia type, and the cell line is derived from a 53-year-old female chronic myelogenous leukemia patient in blast cris ...

s and is sensitive to DNase I, but shows almost no signal for mammalian constraint.

HBB complex

References

Further reading