Promoter-associated proteins of EPAS1 identified by enChIP-MS – A putative role of HDX as a negative regulator

Hamidian, Arash; Vaapil, Marica; Stedingk, Kristoffer von; Fujita, Toshitsugu; Persson, C.; Eriksson, Pontus; Veerla, Srinivas; Preter, Katleen De; Speleman, Franki; Fujii, Hodaka; Påhlman, Sven; Mohlin, Sofie

doi:10.1016/j.bbrc.2018.03.150

Cited by 12 publications

(11 citation statements)

References 21 publications

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“…Along the same line, we used immunohistochemistry to stain cells cultured at normoxia (21%) or hypoxia (1% O 2 ) with the NB100‐132 primary antibody (mouse anti‐HIF‐2α; Novus Biologicals) and as expected only observed HIF‐2α expression at lowered oxygen concentrations (Figure 1G). Together with previous data on these antibodies, 6,9,15,16 these results ensure antibody specificity.…”

Section: Resultssupporting

confidence: 79%

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Hypoxia inducible factor‐2α importance for migration, proliferation, and self‐renewal of trunk neural crest cells

Niklasson

Fredlund

Monni

et al. 2020

Developmental Dynamics

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Background: The neural crest is a transient embryonic stem cell population. Hypoxia inducible factor (HIF)-2α is associated with neural crest stem cell appearance and aggressiveness in tumors. However, little is known about its role in normal neural crest development. Results: Here, we show that HIF-2α is expressed in trunk neural crest cells of human, murine, and avian embryos. Knockdown as well as overexpression of HIF-2α in vivo causes developmental delays, induces proliferation, and selfrenewal capacity of neural crest cells while decreasing the proportion of neural crest cells that migrate ventrally to sympathoadrenal sites. Reflecting the in vivo phenotype, transcriptome changes after loss of HIF-2α reveal enrichment of genes associated with cancer, invasion, epithelial-to-mesenchymal transition, and growth arrest. Conclusions: Taken together, these results suggest that expression levels of HIF-2α must be strictly controlled during normal trunk neural crest development and that dysregulated levels affects several important features connected to stemness, migration, and development. K E Y W O R D S embryogenesis, HIF-2α, migration, neural crest, stem cells, trunk neural crest Camilla U. Niklasson and Elina Fredlund contributed equally to this work.

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Section: Resultssupporting

confidence: 79%

“…Error bars represent SEM, n ≥ 3 biologically independent replicates for each time point HIF-2α expression at lowered oxygen concentrations ( Figure 1G). Together with previous data on these antibodies, 6,9,15,16 these results ensure antibody specificity.…”

Section: Hif-2α Is Expressed In Migratory Trunk Neural Crest Cells supporting

confidence: 85%

Hypoxia inducible factor‐2α importance for migration, proliferation, and self‐renewal of trunk neural crest cells

Niklasson

Fredlund

Monni

et al. 2020

Developmental Dynamics

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“…high levels of HIF2α in non-MYCN amp tumors [135]. Recently even the group that has published the majority of the papers on HIF2α as an oncogenes in NB, published a paper [160] in which they show that EPAS1 is highly expressed in non-MYCN amplified tumors (Fig 2E), however still argue in the paper that HIF2α is oncogenic. Although, it is hard to fully exclude an oncogenic role of HIF2α, however it can be concluded that HIF2α isn't a permanent feature of high-risk NB.…”

Section: Simon Et Al Show An Association Between High Levels Of Hif1αmentioning

confidence: 99%

EPAS1/HIF2α correlates with features of low-risk neuroblastoma and with adrenal chromaffin cell differentiation during sympathoadrenal development

Westerlund

Shi

Holmberg

2019

Biochemical and Biophysical Research Communications

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“…For example, in mouse adipocyte cells the involvement of transcription factors SP1 and SP3 in EPAS1 expression has been suggested [26], while in neuroblastoma cells, phosphatidylinositol 3-kinase (PI3K) and serine/threonine-protein kinase mTORC2 have been demonstrated to regulate its transcription [27]. However, Hamidian et al (2018) [28] identified a set of proteins specifically bound to the EPAS1 promoter region at normoxia in neuroblastoma cells. The majority of these proteins showed decreased binding to the EPAS1 promoter at hypoxia, indicating increased EPAS1 transcription as the result of dissociated promoter-associated factors.…”

Section: Regulation Of Hif2α Transcriptionmentioning

confidence: 99%

Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis

Tomc

Debeljak

2021

IJMS

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Erythropoiesis is regulated by several factors, including the oxygen-sensing pathway as the main regulator of erythropoietin (EPO) synthesis in the kidney. The release of EPO from the kidney and its binding to the EPO receptor (EPOR) on erythrocyte progenitor cells in the bone marrow results in increased erythropoiesis. Any imbalance in these homeostatic mechanisms can lead to dysregulated erythropoiesis and hematological disorders. For example, mutations in genes encoding key players of oxygen-sensing pathway and regulation of EPO production (HIF-EPO pathway), namely VHL, EGLN, EPAS1 and EPO, are well known causative factors that contribute to the development of erythrocytosis. We aimed to investigate additional molecular mechanisms involved in the HIF-EPO pathway that correlate with erythropoiesis. To this end, we conducted an extensive literature search and used several in silico tools. We identified genes encoding transcription factors and proteins that control transcriptional activation or repression; genes encoding kinases, deacetylases, methyltransferases, conjugating enzymes, protein ligases, and proteases involved in post-translational modifications; and genes encoding nuclear transport receptors that regulate nuclear transport. All these genes may modulate the stability or activity of HIF2α and its partners in the HIF-EPO pathway, thus affecting EPO synthesis. The theoretical information we provide in this work can be a valuable tool for a better understanding of one of the most important regulatory pathways in the process of erythropoiesis. This knowledge is necessary to discover the causative factors that may contribute to the development of hematological diseases and improve current diagnostic and treatment solutions in this regard.

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Promoter-associated proteins of EPAS1 identified by enChIP-MS – A putative role of HDX as a negative regulator

Cited by 12 publications

References 21 publications

Hypoxia inducible factor‐2α importance for migration, proliferation, and self‐renewal of trunk neural crest cells

Hypoxia inducible factor‐2α importance for migration, proliferation, and self‐renewal of trunk neural crest cells

EPAS1/HIF2α correlates with features of low-risk neuroblastoma and with adrenal chromaffin cell differentiation during sympathoadrenal development

Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis

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