Globin

Globin production is mainly controlled at the transcription level past a complex interaction of Deoxyribonucleic acid sequences (cis-interim promoters, enhancers, and silencers) and soluble transcription factors (trans-acting factors) that bind to DNA or to one some other to promote or suppress transcription.

From: Rodak'southward Hematology (Sixth Edition) , 2020

Thalassemia

Rick D. Kellerman Physician , in Conn's Electric current Therapy 2021 , 2021

Globin Gene Arrangements

Thalassemia syndromes encompass a spectrum of hemoglobin disorders that ascend from impaired production of globin chains. The genes that encode globins are located in two clusters: the β gene cluster on chromosome eleven and the α gene cluster on chromosome xvi ( Figure 1). The β factor cluster includes the adult globin genes (β and δ) as well as the fetal Aγ and Gγ genes and the embryonic ε gene. The arrangement of the v′ to 3′ sequence of these genes parallels the society of their developmental expression. Functional hemoglobin is a tetramer that includes two α and two β globin units. The α gene cluster includes two fetal/adult α genes (α1 and α2) and the embryonic ζ genes. In the embryo, three hemoglobins are found (ζ2ε2, α2ε2, and ζiiγ2). Fetal hemoglobin (HbF) is composed of two α bondage and two γ chains (αtwoγ2). In adults, the predominant hemoglobin is hemoglobin A (HbA), consisting of ii α chains and two β chains (α2βtwo) (run acrossEffigy 1). Hemoglobin A2, consisting of ii α chains and two δ chains (αtwoδ2), is a normal variant in adults and typically represents less than iii% of the total hemoglobin (encounterFigure 1).

In β-thalassemia, there is diminished production of β globin genes, resulting in an excess of α globin chains. Conversely, in α-thalassemia in that location is dumb production of α globin genes, resulting in an backlog of β globin chains. This imbalance of globin product is variable, and the degree of accumulation of unpaired globin chains is directly related to the severity of the disease phenotype. The genetic footing of thalassemia is heterogeneous, and several hundred mutations accept been identified. These mutations may impact any level of globin gene expression, including arrangement of the globin gene circuitous, cistron deletion, splicing, transcription, translation, and protein stability. In full general, β-thalassemia occurs equally a result of mutations, whereas α-thalassemia occurs every bit a result of factor deletion.

It has been estimated that in that location are 270 million carriers of thalassemia in the world, including 80 one thousand thousand β-thalassemia carriers. The frequency of β-thalassemia carriers is highest in the malarial tropical and subtropical regions of Asia, the Mediterranean, and the Centre East. The term thalassemia, derived from Greek, refers to the Mediterranean Sea. This distribution is secondary to the selective advantage of heterozygotes against malaria. β-Thalassemia is subdivided into major, intermedia, and minor types (Tabular array ane). α-Thalassemia is classified into iv syndromes: α-thalassemia trait 2 (loss of one α globin gene [αα/α−]);α-thalassemia trait one, also referred to as α-thalassemia pocket-size (loss of 2 α globin genes [αα/− − or α−/α−]); hemoglobin H (HbH) disease (loss of iii alleles [α−/− −]); and hemoglobin Barts hydrops fetalis (loss of all four α globin loci [− −/− −]).

Erythrocyte disorders

Courtney Lawrence , Emily Riehm Meier , in Biochemical and Molecular Basis of Pediatric Illness (Fifth Edition), 2021

Genetic structure and synthesis of normal hemoglobins

The globin proteins are highly conserved amongst mammals, all derived from a single ancestral globin cistron that arose over 500 meg years agone [3]. Man hemoglobin, the nigh widely studied of all of the globin proteins, is composed of two alpha-like globin bondage, ii beta-like globin bondage, and 4 heme moieties. The heme groups comprise iron atoms which let hemoglobin to transport oxygen from the lungs to the tissues [iii]. The genes encoding the blastoff-like chains [either zeta (ζ) globin or alpha (α) globin] are located on chromosome sixteen. Chromosome eleven encodes the beta-like chains: epsilon (ε), gamma (γ), delta (δ), and beta (β). Globin concatenation expression follows a stepwise progression from the 5′ to three′ end of the alpha and beta-globin factor clusters (come across Fig. 17.1). Two major switches occur in hemoglobin ontogenesis: from embryonic [Gower 1 (ζ2ε2), Gower 2 (α2εii), and Portland (ζiiγii)] to fetal hemoglobin (HbF, α2γ2) and from fetal hemoglobin to adult hemoglobin (HbA, αtwoβtwo) [4]. Fetal to adult hemoglobin switching is largely a postnatal phenomenon with current evidence suggesting that binding of repressor proteins to the γ globin promoter region is likely critical in the switching machinery [v,vi]. This mechanism remains an active area of research given its importance in developing therapies that induce HbF and potentially mitigate symptoms associated with beta hemoglobinopathies.

Fig 171

Fig. 17.ane. Genomic structure of the clusters of the α- and β-like globin genes. The α-like gene cluster is institute on chromosome xvi and is ii-thirds the size of the β-like cistron cluster (institute on chromosome xi). The of import control elements HS-40 and locus-control region (LCR) are shown and described in the text. The diverse hemoglobin tetrameric species that form from the expression of functional genes during embryogenesis, fetal development, and adulthood are shown.

Reproduced with permission from A.Northward. Schechter, Hemoglobin inquiry and the origins of molecular medicine. Blood 2008;112:3927-3938 [3].

Very early during embryonic development ζ globin, located 5′ to the two α genes (α2 and α1) on the alpha globin cluster, is the first alpha-like globin produced. However, only subsequently 8 weeks of gestation, alpha globin becomes the predominant blastoff-like globin produced, though ζ globin has been detected in healthy newborns [7]. Similarly, ε globin is the outset beta-like globin transcribed. This is followed by γ globin product beginning at 2 months of gestation. Beta globin production starts in utero simply does not get the predominant globin produced until well-nigh 6 months of age. The hemoglobin switching process appears programmed with gestational development, such that infants born prematurely show HbF and HbA synthesis patterns that progress to match that of term infants past the time they reach corrected term gestational historic period [8]. Delta globin production remains depression until approximately ane year of historic period when it reaches developed levels [9].

From weeks iii through viii of gestation, the yolk sac is the master site of erythropoiesis. Gower one(ζtwoεtwo), Gower two (α2ε2), and Portland (ζtwoγtwo) are the main embryonic hemoglobins produced early in gestation [7]. After the 8th gestational week, red cell production shifts from the yolk sac to the fetal liver. Concurrently, fetal hemoglobin (α2γ2) becomes the predominant hemoglobin produced. Two γ genes exist, Gγ and Aγ, which differ by only one amino acid. Gγ contains a glycine, while Aγ has an alanine at position 136. Thouγ production is triple that of Aγ at birth, though the ratio of production in good for you adults varies widely. Compared to HbA (αtwoβtwo), HbF has an increased oxygen affinity which promotes oxygen delivery from the placenta to the fetus. After delivery, hematopoiesis shifts from the fetal liver to the bone marrow. Postnatally, HbF levels rapidly drop to less than ii% inside the get-go year of life [10,11]. After the switch, HbA becomes the predominant hemoglobin (95%–97%) with HbA2 (αtwoδtwo) comprising the remaining 2.5%–3.5% [9].

Globin chain product is closely regulated by a variety of transcription factors. Production of alpha- and beta-like globins is directed by sequences located 5–40 kb upstream of the gene loci [12]. The enhancer sequences for each globin [the hypersensitivity site-twoscore (HS-40) on the alpha-globin locus and the beta-globin locus-command region (LCR)] display the same Dna-binding sites. The LCR, composed of five DNAse I hypersensitive sites (HS), regulates the transcription of beta globin bondage in a developmental sequence. The importance of LCR in beta globin production is exemplified by the fact that beta thalassemia occurs when the LCR is deleted or absent [12,thirteen]. Other beta globin gene promoters include the TATA, CCAAT, and CACCC boxes. These are located seventy–100 bases upstream from the gene and are required to maximize beta globin production [xiv]. GATA-i, one of the first transcription factors recognized as important in globin gene synthesis, is ubiquitous in the beta globin gene regulatory elements [15]. Kruppel-similar factor 1 (KLF-1, formerly EKLF), a transcription factor with erythroid lineage specificity, binds the CACCC box and activates transcription of the beta globin gene. KLF-ane preferentially binds to the beta globin gene promoter over the γ globin promoter [14,16] and may play a role in the last steps of HbF silencing in humans [14,17]. The absence of KLF-1 is lethal in the fetus considering of the lack of beta globin gene product.

The 8 globin genes that are nowadays in humans each contain three exons and 2 introns. The introns are spliced from mRNA prior to translation. In addition to the eight functional globin genes, the globin cistron clusters on both chromosome eleven and 16 comprise pseudogenes which take no known function. There are four pseudogenes inside the alpha globin cluster, three are located between ζ and α2 and the quaternary is located 3′ to the α1 locus [18]. Conversely, only one beta globin pseudogene (HBBP1) has been identified between Aγ and δ. HBBP1 appears to take an important function in maintaining the chromatin compages that allows for the interaction of LCR with globin genes at various stages of evolution [xix].

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The Molecular Basis of Genetic Disease : General Principles and Lessons from the Hemoglobinopathies

Robert L. Nussbaum Physician, FACP, FACMG , in Thompson & Thompson Genetics in Medicine , 2016

Developmental Expression of Globin Genes and Globin Switching

The expression of the various globin genes changes during development, a procedure referred to every bit globin switching (run intoFig. 11-3B). Note that the genes in the α- and β-globin clusters are arranged in the same transcriptional orientation and, remarkably, the genes in each cluster are situated in the same order in which they are expressed during development. The temporal switches of globin synthesis are accompanied by changes in the principal site of erythropoiesis (encounterFig. xi-3B). Thus the iii embryonic globins are made in the yolk sac from the tertiary to eighth weeks of gestation, only at approximately the fifth week, hematopoiesis begins to movement from the yolk sac to the fetal liver. Hb F (αtwoγii), the predominant hemoglobin throughout fetal life, constitutes approximately seventy% of full hemoglobin at nativity. In adults, notwithstanding, Hb F represents less than a few per centum of the total hemoglobin, although this can vary from less than one% to approximately 5% in different individuals.

β-chain synthesis becomes meaning near the time of birth, and past three months of age, almost all hemoglobin is of the adult type, Hb A (αtwoβ2) (run acrossFig. xi-3B). In diseases due to mutations that subtract the abundance of β-globin, such every bit β-thalassemia (encounter subsequently department), strategies to increase the commonly small-scale amount of γ-globin (and therefore of Hb F (α2γii)) produced in adults are proving to be successful in ameliorating the disorder (seeAffiliate xiii).

Investigation of abnormal haemoglobins and thalassaemia

Barbara Wild , Barbara J. Bain , in Dacie and Lewis Applied Haematology (Tenth Edition), 2006

Globin Chain Electrophoresis

Principle

Electrophoresis of globin chains 36,37 is used to plant which chain is affected (i.east., α or β or γ). This information is useful in further predicting the nature of the variant and possible interactions.

Alkaline Globin Chain Electrophoresis, pH 8.0

Reagents

Add 2 ml concentrated muriatic acid to 98 ml of acid acetone that has been cooled to −20°C. The reagent should be prepared just before use.

Buffer

Stock buffer. Diethyl barbituric acrid, 36.viii g, 1 mol/l sodium hydroxide solution, 120 ml. Deliquesce the diethyl barbituric acrid in 1500 ml of humid distilled h2o. Allow to absurd to room temperature and adjust pH to 8.0 with 1 mol/50 NaOH. Make up to a final book of ii litres. Store at room temperature.

Working buffer. Stock buffer, 600 ml, urea, 360 g, DL-dithiothreitol (DTT), 60 mg. Prepare on day of use.

Stain solvent. Glacial acetic acid, 400 ml, methanol, 1800 ml, distilled water, 1800 ml.

Amido black stain. Stain solvent, 1 litre, amido black (Naphthol black), 0.4 g.

Diethyl ether.

Equipment

Electrophoresis tank and power pack. Whatever horizontal electrophoresis tank that will allow a bridge gap of vii cm. A direct electric current power supply capable of delivering 350 V at 50 mA is suitable for both cellulose acetate and citrate agar electrophoresis.

Wicks of filter or chromatography paper.

Blotting paper.

Applicators. These are available from most manufacturers of electrophoresis equipment, but fine microcapillaries are as well satisfactory.

Cellulose acetate membranes. Plastic backed membranes (7.6 × half-dozen.0 cm) are recommended for ease of use and storage.

Staining equipment.

Drinking glass centrifuge tubes.

Method

1.

With a whole blood sample, wash the cells twice in ix g/l NaCl and lyse by adding an equal volume of water to the washed, packed cells. Purified haemolysates are as well suitable.

2.

Add together xx ml of the haemolysate to 10 ml of cold acrid acetone in a glass centrifuge tube, dispersing the haemoglobin rapidly by flushing with the pipette.

three.

Centrifuge at 700 g for 10 min in a refrigerated centrifuge.

4.

With a Venturi pump, remove all merely a small amount of the supernatant acid acetone. Avert contamination of the pipette by the globin pellet. Resuspend the globin pellet by means of a vortex mixer.

5.

Add 10 ml of cold acetone forcefully to thoroughly disperse the globin.

6.

Centrifuge at 700 g for 5 min in a refrigerated centrifuge.

seven.

Repeat steps four to six.

8.

Remove the acetone and resuspend the globin. Add 10 ml of diethyl ether and arouse forcefully to disperse the globin.

9.

Centrifuge at 700 chiliad for five min in a refrigerated centrifuge.

x.

Dry the globin to a foam-coloured pellet past sucking air over the globin with a Pasteur pipette attached to a Venturi pump. The globin tin can be stored at −20°C until tested. Deliquesce each of the globin pellets in 200 ml of working buffer before employ.

11.

With the power supply disconnected, prepare the electrophoresis tank by placing 100 ml of working buffer in each of the outer buffer compartments. Soak two paper wicks and identify ane along each of the dividers.

12.

Carefully lower cellulose acetate plate(s) into a reservoir of working buffer. Permit to soak for at least 1 hour before apply.

thirteen.

Place 5 μl of the patient and control globin samples in a sample well plate.

14.

Remove the cellulose acetate from the working buffer and absorb between two layers of clean blotting newspaper until almost dry.

15.

Load the sample applicator and apply onto make clean blotting paper; reload and employ onto the cellulose acetate in the primal position.

16.

Place the cellulose acetate plate in the electrophoresis tank with two microscope slides across each plate to maintain contact with the wicks.

17.

Electrophorese at 200 V for 1 hour.

eighteen.

On completion of the electrophoresis, place the plate into the amido black stain solution and leave to set and stain for x min.

19.

Destain the plates in stain solvent, leaving for 5–10 min in each reservoir until the background is clear.

xx.

Remove the plates from the solvent and let to dry out betwixt two clean sheets of blotting paper.

Estimation and Comments

Normal α chains drift toward the cathode, and normal β chains migrate toward the anode. The relative migration of globins from the test samples are compared to both the known controls and the mobilities of the test samples on cellulose acetate electrophoresis. The relative mobilities of some abnormal α and β bondage are shown in Figure 12.10.

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F – Laboratory Tests and Interpretation of Results

Fred F. Ferri Doctor, FACP , in Ferri's Clinical Advisor 2022 , 2022

Fecal Globin Immunochemical Exam

Normal

Negative. This test is performed by immunochromatography on a cellulose strip that has been impregnated with various antibodies. The test uses a minor amount of toilet h2o as the specimen and is placed onto absorptive pads of card similar to traditional occult claret (OB) card. There is no directly treatment of stool. This test is specific for the globin portion of the hemoglobin molecule, which confers lower GI bleeding specificity. It specifically detects blood from the lower GI tract; guaiac tests are not lower GI specific. It is more sensitive than typical Hemoccult test (detection limit 50 mcg Hb/chiliad feces versus >500 mcg Hb/g carrion for Hemoccult). Information technology has no dietary restrictions and gives no fake-positives due to plant peroxidases and scarlet meats. It has no medication restrictions. Iron supplements and NSAIDs do not cause false positives. Vitamin C does not cause false-negatives.

Positive in

Hemoglobin metabolism

Catherine N. Otto , in Rodak'southward Hematology (Sixth Edition), 2020

Globin structure

The iv globin chains comprising each hemoglobin molecule consist of two identical pairs of different polypeptide chains, 141 to 146 amino acids each. Variations in amino acrid sequences give rise to unlike types of polypeptide bondage. Each chain is designated by a Greek alphabetic character ( Table vii.1). one , 3

Each globin chain is divided into viii helices separated by seven nonhelical segments (Figure 7.3). 3 The helices, designated A to H, incorporate subgroup numberings for the sequence of the amino acids in each helix and are relatively rigid and linear. Flexible nonhelical segments connect the helices, equally reflected past their designations: NA for the sequence betwixt the N-terminus and the A helix, AB between the A and B helices, and so forth, with BC, CD, DE, EF, FG, GH, and finally HC between the H helix and the C-terminus. three

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Investigation of abnormal haemoglobins and thalassaemia

Barbara J. Wild , Barbara J. Bain , in Dacie and Lewis Practical Haematology (Eleventh Edition), 2012

Sample Requirements

Blood samples for globin chain synthesis accept to exist fresh (received within a few hours of collection) and transported at 4°C. Blood samples for Dna assay can exist sent by overnight delivery without refrigeration only must be processed, at the latest, within 3 days of collection. From each parent, 10 ml of blood in EDTA or heparin is required. If brake fragment length polymorphism (RFLP) linkage analysis is required, the following additional samples are needed: blood from either a homozygous normal or afflicted kid, or from a heterozygous child and one set of grandparents, or, if no child is available, claret from both sets of grandparents. The samples must exist carefully and conspicuously labelled and the family tree must be drawn. Particulars of all haematological tests must be given.

Chorionic villus samples must exist dissected costless of any maternal tissue and sent past urgent overnight delivery in tissue culture medium or, preferably, in a special buffer obtainable from the Dna diagnostic laboratory. Amniotic fluid samples (15–20 ml are needed) and must be received within 24 h of drove. If a longer transit fourth dimension is unavoidable, the amniocytes should exist resuspended in tissue culture medium.

The laboratory performing Dna assay for disorders of globin chain synthesis must be given accurate information on the precise ethnic origin of family members and so that optimal use is made of the DNA available for diagnosis.

It is essential that follow-upwards information are obtained on all cases that have undergone fetal diagnosis. This should include tests on cord blood or heel prick sample at birth and a examination at 6 months to confirm the carrier state. Whenever possible, Dna assay of the kid'south globin genes should be carried out.

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Disorders of abnormal hemoglobin

Reena Das , Prashant Sharma , in Clinical Molecular Medicine, 2020

Abstract

Hemoglobin abnormalities include globin concatenation defects resulting in the thalassemia syndromes as well as structurally and functionally variant hemoglobins (Hbs) that may be unstable, cause sickling, methemoglobinemia, or have loftier or depression oxygen affinity. Globally, thalassemias represent the commonest monogenic disorders that occur in high frequencies in the malaria belt. β Thalassemia trait is characterized by high HbA ii, and β-globin (HBB) mutations can be detected by reverse dot-blot analysis, amplification refractory mutation system-PCR or direct Sanger sequencing. α-Globin (HBA1 and HBA2) genes' defects are most accurately identified by molecular tests, with the exception being HbH disease that yields a "golf-ball" appearance in HbH grooming, preintegration peaks on high-performance liquid chromatography, and a fast-moving ring on alkaline pH electrophoresis. Multiplex gap-PCR or multiplex ligation-dependent probe amplification place common α-globin gene deletions while nondeletional α thalassemia is detected by specific α-globin gene sequencing. The structural variants include HbS (sickle Hb), HbE, and HbC among others and pose region and ethnic group–specific problems. Disorders of heme synthesis are a relatively smaller group that however shows characteristic clinical and laboratory findings.

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iPSC-derived erythroid cells

Daniel C.J. Ferguson , ... Jan Frayne , in Contempo Advances in iPSC-Derived Cell Types, 2021

The globin expression profile of iPSC-derived erythroid cells

Erythroid cells cultured from iPSCs express predominantly embryonic and fetal globins. The globin expression patterns of iPSC-derived erythroid cells from various studies are summarized in Table i.1. Interestingly, globin switching of nucleated iPSC-erythroid cells post-obit transplantation in vivo has been reported and implies that transition to adult globin expression depends on contextual cues (Kobari et al., 2012; Doulatov et al., 2013), although the mechanism is unknown. Yet, developed erythroid cell equivalent levels of HbA are withal not achieved. Co-culture during erythroid differentiation has also been suggested to increase adult globin expression in iPSC-derived erythroid cells. Yang et al. (2014) showed that after 14 days of erythroid co-civilization with OP9, 44% were HbF+HbA+ by flow cytometry compared to sixteen.four% for cells not in co-culture. However, just effectually ane% of the co-cultured erythroid cells expressed but HbA and absolute levels of HbA were not reported. Fujita et al. (2016) likewise used OP9 co-civilization and showed that iPSC-derived cells could produce effectually xv% β-globin transcript as a proportion of total β-type globins. Ochi et al. (2014) co-cultured iPSC-derived erythroid cells with C3H10T1/two cells (a mouse embryonic fibroblast jail cell line) and found the proportion of cells co-expressing γ-, ε-, and β-globin, measured using multicolor flow cytometry, increased during differentiation, although the level of β- was still lower than that of γ- and ε-globin. Extended HSC cultures may also cause iPSC-derived cells to have a more developed globin expression profile by increasing developmental maturity: Olivier et al. (2019) generated iPSC-derived erythroid cells with a predominantly fetal globin expression profile, but with β-globin bookkeeping for 15.5% of total β-type globins, using a chemically-defined erythroid culture system. This relatively loftier β-globin level was not observed when a shorter HSC culture was performed (Olivier, 2019).

Of annotation, when testing globin levels, the methods used are an of import consideration (see Tabular array one.1 for different methods used by different studies). RT-qPCR is a frequent choice along with other methods to measure factor expression; however, transcript levels do not directly equate to poly peptide levels (Moore and von Lindern, 2018). Antibody-based techniques, such as flow cytometry and western blot, can endure from cross-reactivity and a narrow dynamic range of the antibodies. Antibodies to the same and unlike globins may also take dissimilar affinities and thus give different signal intensities, exacerbated when secondary antibodies are used for signal amplification, making direct comparison between levels of unlike globins and between globin levels in different studies difficult. Chromatography techniques such as reverse-phase liquid chromatography (RPLC) or high-functioning liquid chromatography (HPLC) can exist used to mensurate the native globin proteins and are therefore the golden standard for determining hemoglobin composition. Extra specificity can be accomplished past confirming the chromatogram peaks using mass spectrometry.

Decreased levels of key transcription factors may be responsible for the fetal/embryonic globin expression pattern of iPSC-derived erythroid cells. In item, BCL11A, SOX6, and KLF1, all factors of import for an adult globin expression profile, are lower in iPSC versus primary erythroid cells (Trakarnsanga et al., 2014; Ochi et al., 2014; Yang et al., 2017; Merryweather-Clarke et al., 2016). Ochi et al. (2014) showed that β-globin levels could be increased by expression of BCL11A-L in iPSC-derived erythroid cells. Similarly, Trakarnsanga et al. (2014) showed ectopic expression of BCL11A-XL in HiDEP-1 cells, immortalized erythroid cells differentiated from iPSCs (see later), induced a switch from embryonic and fetal to developed globin expression. These studies, as with the in vivo studies earlier, prove that iPSC-derived erythroid cells are capable of an adult erythroid prison cell globin phenotype.

Overall, it appears iPSC-derived erythroid cells achieve predominantly a definitive erythroid phenotype. They are, even so, more closely aligned to fetal than developed erythroid cells, as demonstrated by Trakarnsanaga et al. (2014), expressing predominantly fetal only with some embryonic globin, indicative of a small primitive moving ridge as described by Hansen et al. (2018). Supporting this, studies accept shown that iPSC-derived erythroid cells can produce a functional hemoglobin tetramer that binds ligands (e.g., carbon monoxide or oxygen) similarly to fetal or CB erythroid cells (Lapillonne et al., 2010; Kobari et al., 2012).

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Down's syndrome-Related Myeloid Proliferations

In Diagnostic Pathology: Molecular Oncology, 2016

Normal Function of GATA1

•

Canonical name: GATA binding protein 1 (globin transcription factor ane)

•

HGNC_ID: 4170

•

Gene locus: Xp11.23

•

7.7 kb

•

Encodes transcription gene that binds to specific DNA sequences

○

Name GATA1 derives from protein's recognition of sequences that incorporate motif G-A-T-A

•

Binding of GATA1 poly peptide modulates transcription of associated genes

•

Regulation by GATA1 is important in normal erythropoiesis and megakaryopoiesis

•

GATA1 encompasses 6 exons

○

Use of translation get-go site in exon 2 results in production of total-length GATA1 protein

▪

This form of the protein predominates in normal cell

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