The Structure and Organization of the Human Erythroid Anion Exchanger (AE1) Gene

Sahr, Kenneth E.; Taylor, William M.; Daniels, Brian P.; Rubin, Hillard; Jarolím, Petr

doi:10.1006/geno.1994.1658

Cited by 51 publications

(35 citation statements)

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“…The gene has been mapped to chromosome 17q21-q22 and consists of 20 exons separated by 19 introns, spanning 17 kb in all (Showe et al, 1987;Sahr et al, 1994;Schofield et al, 1994). Basal promoter activity of the AE1 gene was detected in erythroid and non-erythroid cells, and expression of AE1 mRNA was identified in various species and tissues (Kudrycki and Shull, 1989;Kudrycki et al, 1990;Richards et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells

Zhang

et al. 2010

Oncogene

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Anion exchanger-1 (AE1), an erythroid-specific membrane protein, mediates the Cl À /HCO À 3 exchange across the plasma membrane and regulates intracellular pH. We have found that AE1 was unexpectedly expressed in gastric cancer cells and participated in the tumorigenesis of the cancer. Here, we focus on the induction of AE1 expression and its role in gastric carcinogenesis as well as in the differentiation of K562 cells. The results show that expression of AE1 is not related to genetic mutation or the mRNA level, but rather, that it is modulated by miR-24. miR-24 decreases the expression of AE1 through binding to the 3 0 UTR of AE1 mRNA. Transfection of an miR-24 into gastric cancer cells reduced the elevation of the AE1 protein, which resulted in return of AE1-sequestrated p16 to the nucleus, thereby inhibiting proliferation of the cells. Furthermore, the miR-24 inhibitor cooperated with hemin to induce the expression of AE1 in K562 cells and differentiation of the cells, which is consistent with results obtained from the cells cultured at pH 7.6 or from forced stable expression of AE1. These findings establish a novel regulation of miR-24-related AE1 expression in gastric carcinogenesis and erythropoiesis.

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Section: Introductionmentioning

confidence: 99%

Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells

Zhang

et al. 2010

Oncogene

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“…Indeed, a considerable number of erythroid genes possess alternative first exons. These include the heme biosynthesis enzymes 5-aminolevulinate dehydratase (36), porphobilinogen deaminase (37) and uroporphyrinogen III synthase (38), the transcription factors GATA1 (11), GATA2 (39,40), and NF-E2 p45 (41,42), and also membrane protein Band 3 (43). The first exons and their affiliated promoters are often utilized to support spatiotemporal gene expression.…”

Section: Discussionmentioning

confidence: 99%

Loss of the Gata1 Gene IE Exon Leads to Variant Transcript Expression and the Production of a GATA1 Protein Lacking the N-terminal Domain

Kobayashi

Shimizu

Kikuchi

et al. 2010

Journal of Biological Chemistry

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GATA1 is essential for the differentiation of erythroid cells and megakaryocytes. The Gata1 gene is composed of multiple untranslated first exons and five common coding exons. The erythroid first exon (IE exon) is important for Gata1 gene expression in hematopoietic lineages. Because previous IE exon knockdown analyses resulted in embryonic lethality, less is understood about the contribution of the IE exon to adult hematopoiesis. Here, we achieved specific deletion of the floxed IE exon in adulthood using an inducible Cre expression system. In this conditional knock-out mouse line, the Gata1 mRNA level was significantly down-regulated in the megakaryocyte lineage, resulting in thrombocytopenia with a marked proliferation of megakaryocytes. By contrast, in the erythroid lineage, Gata1 mRNA was expressed abundantly utilizing alternative first exons. Especially, the IEb/c and newly identified IEd exons were transcribed at a level comparable with that of the IE exon in control mice. Surprisingly, in the IE-null mouse, these transcripts failed to produce full-length GATA1 protein, but instead yielded GATA1 lacking the N-terminal domain inefficiently. With low level expression of the short form of GATA1, IE-null mice showed severe anemia with skewed erythroid maturation. Notably, the hematological phenotypes of adult IE-null mice substantially differ from those observed in mice harboring conditional ablation of the entire Gata1 gene. The present study demonstrates that the IE exon is instrumental to adult erythropoiesis by regulating the proper level of transcription and selecting the correct transcription start site of the Gata1 gene.

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“…Preliminary studies demonstrated that the erythroid AE1 promoter was contained within 350 bp of the mRNA start site (20,21,35,36). A truncated AE1 isoform originating from an alternate promoter located in exon 3 is expressed at high levels in kidney cells and at very low levels in erythroid cells (19,21,28,35).…”

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confidence: 99%

Variegated Expression from the Murine Band 3 (AE1) Promoter in Transgenic Mice Is Associated with mRNA Transcript Initiation at Upstream Start Sites and Can Be Suppressed by the Addition of the Chicken β-Globin 5′ HS4 Insulator Element

Frazar¹,

Weisbein²,

Anderson³

et al. 2003

Molecular and Cellular Biology

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The anion exchanger protein 1 (AE1; band 3) is an abundant erythrocyte transmembrane protein that regulates chloride-bicarbonate exchange and provides an attachment site for the erythrocyte membrane skeleton on the cytoplasmic domain. We analyzed the function of the erythroid AE1 gene promoter by using run-on transcription, RNase protection, transient transfection, and transgenic mouse assays. AE1 mRNA was transcribed at a higher level and maintained at a higher steady-state level than either ankyrin or ␤-spectrin in mouse fetal liver cells. When linked to a human ␥-globin gene, two different AE1 promoters directed erythroidspecific expression of ␥-globin mRNA in 18 of 18 lines of transgenic mice. However, variegated expression of ␥-globin was observed in 14 of 18 lines. While there was a significant correlation between transgene copy number and the amount of ␥-globin mRNA in all 18 lines, the transgene mRNAs initiated upstream of the start site of the endogenous AE1 mRNA. Addition of the insulator element from 5HS4 of the chicken ␤-globin cluster to the AE1/␥-globin transgene allowed position-independent, copy-number-dependent expression at levels similar to the AE1 transcription rate in six of six lines of transgenic mice. The mRNA from the insulated AE1/␥-globin transgene mapped to the start site of the endogenous AE1 mRNA, and ␥-globin protein was expressed in 100% of erythrocytes in all lines. We conclude that the chicken ␤-globin 5HS4 element is necessary for full function of the AE1 promoter and that position effect variegation is associated with RNA transcription from the upstream start sites.

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The Structure and Organization of the Human Erythroid Anion Exchanger (AE1) Gene

Cited by 51 publications

References 0 publications

Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells

Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells

Loss of the Gata1 Gene IE Exon Leads to Variant Transcript Expression and the Production of a GATA1 Protein Lacking the N-terminal Domain

Variegated Expression from the Murine Band 3 (AE1) Promoter in Transgenic Mice Is Associated with mRNA Transcript Initiation at Upstream Start Sites and Can Be Suppressed by the Addition of the Chicken β-Globin 5′ HS4 Insulator Element

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