Identification of an enhancer and an alternative promoter in the first intron of the alpha-fetoprotein gene

Scohy, Sophie; Gabant, Philippe; Szpirer, Claude; Szpirer, Josiane

doi:10.1093/nar/28.19.3743

Cited by 35 publications

(30 citation statements)

References 47 publications

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“…Variant AFP transcripts identified in rodents were expressed preferentially in hepatic or yolk sac cells (24,25). These suggest that the vAFP transcripts in the human hematopoietic cells are different from ones identified in rat or in mouse not only in their molecular structures, but also in their expression pattern.…”

Section: Discussionmentioning

confidence: 84%

“…Interestingly, all variant forms of AFP reported in the previous studies and this study use unique first exons. Because the different usage of the first exon suggests that the vAFP expression is dependent on a unique promotor (24,25), further studies are required to elucidate the hematopoietic cell-specific promotor of vAFP.…”

Section: Discussionmentioning

confidence: 99%

“…2B). Recently, it has been reported that an AFP isoform using a new exon located in intron 1 is expressed preferentially in the yolk sac and fetal liver in the mouse (25). However, no detectable amplified band in the PCR using an intron 1-specific 5Ј-primer (data not shown) suggested that the human vAFP transcripts in hematopoietic cells are novel isoforms of AFP.…”

Section: Variant Afp Mrna Expressed In K562 a Human Erythroleukemia mentioning

confidence: 95%

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Variant Forms of α-Fetoprotein Transcripts Expressed in Human Hematopoietic Progenitors

Kubota¹,

Storms²,

Reíd³

2002

Journal of Biological Chemistry

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Hematopoietic stem cells have been identified as multipotent cells that give rise to all adult hematopoietic lineages. Although the hematopoietic lineage is derived from the mesodermal germ layer in the embryo, recent data suggest that bone marrow cells with an antigenic profile consistent with that of hematopoietic stem cells can also differentiate to cell types of the endodermal lineages, such as hepatocytes. However, the molecular mechanisms associated with these events are entirely unknown. For decades, ␣-fetoprotein (AFP) has been used as a differentiation marker for endodermal cells, because it was thought that the transcription of AFP mRNA is tightly regulated in a developmental and tissue-specific process. In this report we describe two new variant forms of AFP transcripts in human hematopoietic progenitors that are not expressed in mature cells. The variant AFP (vAFP) cDNA sequences isolated from a multipotent hematopoietic cell line, K562, revealed that the vAFP differed from the authentic transcript, consisting of 15 exons, by replacing exon 1 of AFP with one or two exons located in the 5-untranslated region of the AFP gene. In addition to the K562 cell line, vAFP transcripts were detected in normal bone marrow, thymus, and brain but were not detected in normal spleen, intestine, liver, or the hepatocellular carcinoma cell line, HepG2. This suggests expression in normal hematopoietic progenitors. This hypothesis was confirmed by the finding that CD34 ؉ Lin ؊ hematopoietic progenitor cells purified from cord blood by flow cytometric sorting also expressed the variant transcripts. These results suggest that some hematopoietic progenitors are in a state that permits them to express certain types of transcripts that have been considered unique to endoderm.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Variant Afp Mrna Expressed In K562 a Human Erythroleukemia mentioning

confidence: 95%

See 1 more Smart Citation

Variant Forms of α-Fetoprotein Transcripts Expressed in Human Hematopoietic Progenitors

Kubota¹,

Storms²,

Reíd³

2002

Journal of Biological Chemistry

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“…The expression of the Afp-GFP transgene within a subpopulation of liver cells may reflect heterogeneity in the onset and level of expression. In addition, the constructs generated for this study lacked an intronic enhancer and alternative promoter known to contribute to Afp expression in the yolk sac and fetal liver (Scohy et al, 2000;Gabant et al, 2002).…”

Section: Endoderm Specificity Of Gfp Expressionmentioning

confidence: 99%

Tg(Afp‐GFP) expression marks primitive and definitive endoderm lineages during mouse development

Kwon

Fraser

Eakin

et al. 2006

Developmental Dynamics

100

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“…5 and 6). More recently it has been shown that the first intron of the Afp gene contains an enhancer and an alternative promoter called P2 (7). The genes of the albumin family are linked in the mammalian genomes, and this conserved organization has been proposed to be important for the developmental expression switch of the genes of the family after birth (8).…”

mentioning

confidence: 99%

Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility

Gabant

Forrester

Nichols

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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The alpha-fetoprotein gene (Afp) is a member of a multigenic family that comprises the related genes encoding albumin, alphaalbumin, and vitamin D binding protein. The biological role of this major embryonic serum protein is unknown although numerous speculations have been made. We have used gene targeting to show that AFP is not required for embryonic development. AFP null embryos develop normally, and individually transplanted homozygous embryos can develop in an AFP-deficient microenvironment. Whereas mutant homozygous adult males are viable and fertile, AFP null females are infertile. Our analyses of these mice indicate that the defect is caused by a dysfunction of the hypothalamic͞ pituitary system, leading to anovulation.A lpha-fetoprotein (AFP) is a serum glycoprotein produced at high levels during fetal life by the liver and the visceral endoderm of the yolk sac and at lower levels by the developing gastrointestinal tract (1, 2). The protein expressed by the embryo is transferred to the maternal blood circulation, and abnormal levels of embryonic AFP in the maternal serum are indicative of spina bifida or Down's syndrome in the fetus (3, 4). The synthesis of AFP decreases dramatically after birth, and only trace amounts are detected in the adult (2). AFP expression has been shown to be regulated by transcriptional mechanisms involving a relatively large promoter (P1) and three distant enhancers (for reviews see refs. 5 and 6). More recently it has been shown that the first intron of the Afp gene contains an enhancer and an alternative promoter called P2 (7). The genes of the albumin family are linked in the mammalian genomes, and this conserved organization has been proposed to be important for the developmental expression switch of the genes of the family after birth (8). Several hypotheses have been proposed for the physiological function of AFP (for reviews see refs. 6, 9, and 10). Because AFP is synthesized during the cell cycle G 1 and S phases, it has been hypothesized that it affects cell growth (11, 12). The observation that AFP is able to bind estrogen led to the suggestion that AFP plays a role in sexual differentiation of the brain by protecting the fetus from the effects of circulating estrogen (13). In addition to binding estrogen, AFP, like albumin, is able to bind other steroids as well as endogenous and exogenous substances such as fatty acids, bilirubin, and various pharmaceutical agents, suggesting that AFP may play a general transportation role (for review see ref. 14). Moreover, because cellular internalization of the protein has been reported, AFP could also interact with cytoplasmic chaperone proteins that normally escort nuclear receptors or transcription cofactors through the cytoplasm toward organelle interfaces (15, 16). AFP has also been proposed to be one protein that protects the embryo against the maternal immune system, on the basis of the observation that addition of purified AFP into the culture of splenic or lymph node mononuclear cells exerts a suppressive effect on ant...

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Identification of an enhancer and an alternative promoter in the first intron of the alpha-fetoprotein gene

Cited by 35 publications

References 47 publications

Variant Forms of α-Fetoprotein Transcripts Expressed in Human Hematopoietic Progenitors

Variant Forms of α-Fetoprotein Transcripts Expressed in Human Hematopoietic Progenitors

Tg(Afp‐GFP) expression marks primitive and definitive endoderm lineages during mouse development

Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility

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