Molecules in focus The NF-E2 transcription factor

Andrews, Nancy C.

doi:10.1016/s1357-2725(97)00135-0

Cited by 84 publications

(56 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results were unexpected because NF-E2 is an essential regulatory element controlling the pathways of heme and globin synthesis [55] [56]. NF-E2 is a heterodimer composed of two subunits of 45kDa and 18kDa protein of the Maf family, respectively.…”

Section: Discussionmentioning

confidence: 99%

HNF4α and NF-E2 are key transcriptional regulators of the murine Abcc6 gene expression

Douet

VanWart

Heller

et al. 2006

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

View full text Add to dashboard Cite

SUMMARYMutations in an ABC transporter gene called ABCC6 are responsible for pseudoxanthoma elasticum (PXE), a rare heritable disease characterized by elastic fiber calcification in skin, ocular and vascular tissues. The presumed function of this ABC transporter is to export metabolites from polarized cells. However, the endogenous substrate(s) are unknown and the exact relationship with elastic fibers is unclear. As ABCC6 is expressed at high level only in liver and kidneys, tissues seemingly unrelated to the PXE phenotype, we explored the transcriptional regulation of the murine Abcc6 gene to define transcriptional regulation conferring tissue specificity and to gather clues on its possible biological function. We cloned 2.9 kb of the mAbcc6 5′-flanking region and several deletion constructs linked to a luciferase reporter gene. We delineated a proximal promoter and a liver-specific enhancer region. We also demonstrated that the proximal region is a TATA-less promoter requiring an intact CCAATbox and Sp1 binding for its basal activity. By using reporter assays and chromatin immunoprecipitations, we showed that HNF4α and surprinsingly, NF-E2, enhanced the mAbcc6 promoter activity. The involvement of both HNF4α and NF-E2 in the mAbcc6 gene regulation suggests that Abcc6 might be involved in a detoxification processes related to hemoglobin or heme.

show abstract

Section: Discussionmentioning

confidence: 99%

HNF4α and NF-E2 are key transcriptional regulators of the murine Abcc6 gene expression

Douet

VanWart

Heller

et al. 2006

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

View full text Add to dashboard Cite

show abstract

“…Unlike in hematopoietic cells, where p45NF-E2 is perceived as a positive regulator (Andrews, 1998), p45NF-E2 must act as a repressor during syncytiotrophoblast development as the absence of p45NF-E2 enhances the expression of Gcm1 and of Gcm1-dependent genes and promotes syncytiotrophoblast formation. Considering the distinct functions of p45NF-E2 during the development of hematopoietic cells (transcriptional activation) and trophoblast cells (transcriptional repression), we propose that p45NF-E2 modulates hematopoietic and trophoblast cell differentiation through at least partially diverse mechanisms.…”

Section: Research Articlementioning

confidence: 99%

p45NF-E2 represses Gcm1 in trophoblast cells to regulate syncytium formation, placental vascularization and embryonic growth

et al. 2011

View full text Add to dashboard Cite

SUMMARYAbsence of the leucine zipper transcription factor p45NF-E2 results in thrombocytopenia, impaired placental vascularization and intrauterine growth restriction (IUGR) in mice. The mechanism underlying the p45NF-E2-dependent placental defect and IUGR remains unknown. Here, we show that the placental defect and IUGR of p45NF-E2 (Nfe2) null mouse embryos is unrelated to thrombocytopenia, establishing that embryonic platelets and platelet-released mediators are dispensable for placentation. Rather, p45NF-E2, which was hitherto thought to be specific to hematopoietic cells, is expressed in trophoblast cells, where it is required for normal syncytiotrophoblast formation, placental vascularization and embryonic growth. Expression of p45NF-E2 in labyrinthine trophoblast cells colocalizes with that of Gcm1, a transcription factor crucial for syncytiotrophoblast formation. In the absence of p45NF-E2, the width of syncytiotrophoblast layer 2 and the expression of Gcm1 and Gcm1-dependent genes (Synb and Cebpa) are increased. In vitro, p45NF-E2 deficiency results in spontaneous syncytiotrophoblast formation, which can be reversed by Gcm1 knockdown. Increased Gcm1 expression in the absence of p45NF-E2 is dependent on enhanced protein acetylation, including post-translational modification of Gcm1. Increasing and inhibiting acetylation in the placenta of wild-type control embryos phenocopies and corrects, respectively, the changes observed in p45NF-E2-deficient embryos. These studies identify a novel function of p45NF-E2 during placental development: in trophoblast cells, p45NF-E2 represses Gcm1 and syncytiotrophoblast formation via acetylation.

show abstract

“…This paradox may be similar to that previously documented for p45. This factor, as a subunit of the heterodimeric NF-E2, is a transcription activator of two globin loci [7] and, yet, p45 (-/-) mice showed no defect in globin gene regulation [46]. We suggest that, similar to the scenario of "functional degeneracy" as proposed for the above observation of p45 (-/-) mice, EKLF is involved in the regulation of both the β-and α-like globin loci in mammals including mice.…”

Section: Discussionmentioning

confidence: 99%

“…The regulation of the mammalian β-like globin switch is achieved through the assembly and interactions of multiple DNA-protein and protein-protein complexes at the locus-control-region (β-LCR) and different globin upstream promoter regions [1][2][3][4]. Among the various nuclear factors participating in the regulation of the mammalian globin switch are those expressed in an erythroid-specific or erythroid-enriched manner, including NF-E2 [7], GATA-1 [8], FOG [9] and EKLF.…”

Section: Introductionmentioning

confidence: 99%

Chromatin-binding in vivo of the erythroid kruppel-like factor, EKLF, in the murine globin loci

et al. 2006

View full text Add to dashboard Cite

EKLF is an erythroid-specific, zinc finger-containing transcription factor essential for the activation of the mammalian beta globin gene in erythroid cells of definitive lineage. We have prepared a polyclonal anti-mouse EKLF antibody suitable for Western blotting and immunoprecipitation (IP) qualities, and used it to define the expression patterns of the EKLF protein during mouse erythroid development. We have also used this antibody for the chromatin-immunoprecipitation (ChIP) assay. EKLF was found to bind in vivo at both the mouse beta-major-globin promoter and the HS2 site of beta-LCR in the mouse erythroleukemia cells (MEL) in a DMSO-inducible manner. The DMSO-induced bindings of EKLF as well as three other proteins, namely, RNA polymerase II, acetylated histone H3, and methylated histone H3, were not abolished but significantly lowered in CB3, a MEL-derived cell line with null-expression of p45/NF-E2, an erythroid-enriched factor needed for activation of the mammalian globin loci. Interestingly, binding of EKLF in vivo was also detected in the mouse alpha-like globin locus, at the adult alpha globin promoter and its far upstream regulatory element alpha-MRE (HS26). This study provides direct evidence for EKLF-binding in vivo at the major regulatory elements of the mouse beta-like globin gene clusters the data also have interesting implications with respect to the role of EKLF-chromatin interaction in mammalian globin gene regulation.

show abstract

Molecules in focus The NF-E2 transcription factor

Cited by 84 publications

References 14 publications

HNF4α and NF-E2 are key transcriptional regulators of the murine Abcc6 gene expression

HNF4α and NF-E2 are key transcriptional regulators of the murine Abcc6 gene expression

p45NF-E2 represses Gcm1 in trophoblast cells to regulate syncytium formation, placental vascularization and embryonic growth

Chromatin-binding in vivo of the erythroid kruppel-like factor, EKLF, in the murine globin loci

Contact Info

Product

Resources

About