Transcriptional regulation of erythropoiesis

Perry, Chava; Soreq, Hermona

doi:10.1046/j.1432-1033.2002.02999.x

Cited by 76 publications

(15 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies of gene expression have formed the conceptual framework for investigating the transcriptional control of erythropoiesis (1,2). Among erythroid transcription factors, GATA-1 is of particular interest, because it is essential for erythropoiesis (3).…”

mentioning

confidence: 99%

The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220

Stumpf

Waskow

Krötschel

et al. 2006

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

View full text Add to dashboard Cite

The Mediator complex forms the bridge between transcriptional activators and RNA polymerase II. Mediator subunit Med1/TRAP220 is a key component of Mediator originally found to associate with nuclear hormone receptors. Med1 deficiency causes lethality at embryonic day 11.5 because of defects in heart and placenta development. Here we show that Med1-deficient 10.5 days postcoitum embryos are anemic but have normal numbers of hematopoietic progenitor cells. Med1-deficient progenitor cells have a defect in forming erythroid burst-forming units (BFU-E) and colony-forming units (CFU-E), but not in forming myeloid colonies. At the molecular level, we demonstrate that Med1 interacts physically with the erythroid master regulator GATA-1. In transcription assays, Med1 deficiency leads to a defect in GATA-1-mediated transactivation. In chromatin immunoprecipitation experiments, we find Mediator components at GATA-1-occupied enhancer sites. Thus, we conclude that Mediator subunit Med1 acts as a pivotal coactivator for GATA-1 in erythroid development.

show abstract

mentioning

confidence: 99%

The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220

Stumpf

Waskow

Krötschel

et al. 2006

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

View full text Add to dashboard Cite

show abstract

“…However, the molecular mechanism of regulating erythropoiesis has not been completely delineated. Most of the studies were focused on the transcription factors to explore the mechanisms of erythropoiesis (4,5). In recent years, several transcription factors were also identified to regulate definitive erythropoiesis in fetal liver during midgestation (6 -11).…”

Section: Real-time Pcr Analyses Showed That In Gpr48mentioning

confidence: 99%

Inactivation of G-protein-coupled Receptor 48 (Gpr48/Lgr4) Impairs Definitive Erythropoiesis at Midgestation through Down-regulation of the ATF4 Signaling Pathway

Song

Luo

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

G-protein-coupled receptors (GPCRs), one of the most versatile groups of cell surface receptors, can recognize specific ligands from neural, hormonal, and paracrine organs and regulate cell growth, proliferation, and differentiation. Gpr48/LGR4 is a recently identified orphan GPCR with unknown functions. To reveal the functions of Gpr48 in vivo, we generated Gpr48 ؊/؊ mice and found that Gpr48 ؊/؊ fetuses displayed transient anemia during midgestation and abnormal definitive erythropoiesis. The dramatic decrease of definitive erythroid precursors (Ter119 pos population) in Gpr48 ؊/؊ fetal liver at E13.5 was confirmed by histological analysis and blood smear assays. Real-time PCR analyses showed that in Gpr48؊/؊ mice both adult hemoglobin ␣ and ␤ chains were decreased while embryonic hemoglobin chains (, ␤H1, and ⑀y) were increased, providing another evidence for the impairment of definitive erythropoiesis. Furthermore, proliferation was suppressed in Gpr48 ؊/؊ fetal liver with decreased c-Myc and cyclin D1 expression, whereas apoptosis was unaffected. ATF4, a key transcription factor in erythropoiesis, was downregulated in Gpr48 ؊/؊ fetal livers during midgestation stage through the cAMP-PKA-CREB pathway, suggesting that Gpr48 regulated definitive erythropoiesis through ATF4-mediated definitive erythropoiesis.Erythropoiesis occurs sequentially in distinct anatomical locations in two different phases during embryogenesis. The earlier phase is defined as primitive erythropoiesis, which, in the mouse, originates from the yolk sac at embryonic day 7.5 (E7.5), 3 and the later phase is definitive erythropoiesis, which was carried out in the fetal liver during midgestation after E12.5. Non-nucleated adult-type red blood cells are first generated in the fetal liver, the primary organ for erythropoiesis during midgestation from E12 to E16 (1). Erythropoiesis then transfers to bone marrow and spleen in the adult (2, 3). However, the molecular mechanism of regulating erythropoiesis has not been completely delineated. Most of the studies were focused on the transcription factors to explore the mechanisms of erythropoiesis (4, 5). In recent years, several transcription factors were also identified to regulate definitive erythropoiesis in fetal liver during midgestation (6 -11). One of the transcription factors is ATF4, which has been shown to regulate cell proliferation in response to a broad spectrum of cell stresses and can be either an activator or a repressor in response to different extracellular signals (12). ATF4 Ϫ/Ϫ mice have been reported to cause defective definitive erythropoiesis, and severe anemia at midgestation (13). Although receptors, such as c-Kit and EPOR, have been well studied in erythropoiesis (14), little is known on the function of G-proteincoupled receptors (GPCRs) in erythropoiesis during development (14, 15).The GPCR family represents the largest and most versatile group of cell surface receptors (16 -18). GPCRs can recognize their ligands, a diverse array of extracellular signals, then transmit th...

show abstract

“…The first committed erythrocyte precursors are the burst-forming unit cells (BFU-E) which differentiate into colony-forming units (CFU-E) and then to proerythroblasts (1). As these cells differentiate further through the basophilic, polychromatic, and orthochromatic erythroblast stages, the nucleus shrinks and is finally shed as the cells become reticulocytes before becoming erythrocytes (2).…”

mentioning

confidence: 99%

“…Analysis of the transcriptional program controlling erythroblast differentiation has identified a number of different transcription factors that are critical to the normal development of erythrocytes (1,2,6). The best studied of these factors regulating erythroid differentiation is GATA-1, a zinc finger transcription factor initially identified as a protein that bound to the globin genes and activated their expression (7).…”

mentioning

confidence: 99%