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Mild dyserythropoiesis and β-like globin gene expression imbalance due to the loss of histone chaperone ASF1B

The expression of the human β-like globin genes follows a well-orchestrated developmental pattern, undergoing two essential switches, the first one during the first weeks of gestation (ε to γ), and the second one during the perinatal period (γ to β). The γ- to β-globin gene switching mechanism inclu...

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Autores principales: Papadopoulos, Petros, Kafasi, Athanassia, De Cuyper, Iris M., Barroca, Vilma, Lewandowski, Daniel, Kadri, Zahra, Veldthuis, Martijn, Berghuis, Jeffrey, Gillemans, Nynke, Cuesta, Celina María Benavente, Grosveld, Frank G., van Zwieten, Rob, Philipsen, Sjaak, Vernet, Muriel, Gutiérrez, Laura, Patrinos, George P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566067/
https://www.ncbi.nlm.nih.gov/pubmed/33066815
http://dx.doi.org/10.1186/s40246-020-00283-3
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author Papadopoulos, Petros
Kafasi, Athanassia
De Cuyper, Iris M.
Barroca, Vilma
Lewandowski, Daniel
Kadri, Zahra
Veldthuis, Martijn
Berghuis, Jeffrey
Gillemans, Nynke
Cuesta, Celina María Benavente
Grosveld, Frank G.
van Zwieten, Rob
Philipsen, Sjaak
Vernet, Muriel
Gutiérrez, Laura
Patrinos, George P.
author_facet Papadopoulos, Petros
Kafasi, Athanassia
De Cuyper, Iris M.
Barroca, Vilma
Lewandowski, Daniel
Kadri, Zahra
Veldthuis, Martijn
Berghuis, Jeffrey
Gillemans, Nynke
Cuesta, Celina María Benavente
Grosveld, Frank G.
van Zwieten, Rob
Philipsen, Sjaak
Vernet, Muriel
Gutiérrez, Laura
Patrinos, George P.
author_sort Papadopoulos, Petros
collection PubMed
description The expression of the human β-like globin genes follows a well-orchestrated developmental pattern, undergoing two essential switches, the first one during the first weeks of gestation (ε to γ), and the second one during the perinatal period (γ to β). The γ- to β-globin gene switching mechanism includes suppression of fetal (γ-globin, HbF) and activation of adult (β-globin, HbA) globin gene transcription. In hereditary persistence of fetal hemoglobin (HPFH), the γ-globin suppression mechanism is impaired leaving these individuals with unusual elevated levels of fetal hemoglobin (HbF) in adulthood. Recently, the transcription factors KLF1 and BCL11A have been established as master regulators of the γ- to β-globin switch. Previously, a genomic variant in the KLF1 gene, identified by linkage analysis performed on twenty-seven members of a Maltese family, was found to be associated with HPFH. However, variation in the levels of HbF among family members, and those from other reported families carrying genetic variants in KLF1, suggests additional contributors to globin switching. ASF1B was downregulated in the family members with HPFH. Here, we investigate the role of ASF1B in γ- to β-globin switching and erythropoiesis in vivo. Mouse-human interspecies ASF1B protein identity is 91.6%. By means of knockdown functional assays in human primary erythroid cultures and analysis of the erythroid lineage in Asf1b knockout mice, we provide evidence that ASF1B is a novel contributor to steady-state erythroid differentiation, and while its loss affects the balance of globin expression, it has no major role in hemoglobin switching.
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spelling pubmed-75660672020-10-20 Mild dyserythropoiesis and β-like globin gene expression imbalance due to the loss of histone chaperone ASF1B Papadopoulos, Petros Kafasi, Athanassia De Cuyper, Iris M. Barroca, Vilma Lewandowski, Daniel Kadri, Zahra Veldthuis, Martijn Berghuis, Jeffrey Gillemans, Nynke Cuesta, Celina María Benavente Grosveld, Frank G. van Zwieten, Rob Philipsen, Sjaak Vernet, Muriel Gutiérrez, Laura Patrinos, George P. Hum Genomics Primary Research The expression of the human β-like globin genes follows a well-orchestrated developmental pattern, undergoing two essential switches, the first one during the first weeks of gestation (ε to γ), and the second one during the perinatal period (γ to β). The γ- to β-globin gene switching mechanism includes suppression of fetal (γ-globin, HbF) and activation of adult (β-globin, HbA) globin gene transcription. In hereditary persistence of fetal hemoglobin (HPFH), the γ-globin suppression mechanism is impaired leaving these individuals with unusual elevated levels of fetal hemoglobin (HbF) in adulthood. Recently, the transcription factors KLF1 and BCL11A have been established as master regulators of the γ- to β-globin switch. Previously, a genomic variant in the KLF1 gene, identified by linkage analysis performed on twenty-seven members of a Maltese family, was found to be associated with HPFH. However, variation in the levels of HbF among family members, and those from other reported families carrying genetic variants in KLF1, suggests additional contributors to globin switching. ASF1B was downregulated in the family members with HPFH. Here, we investigate the role of ASF1B in γ- to β-globin switching and erythropoiesis in vivo. Mouse-human interspecies ASF1B protein identity is 91.6%. By means of knockdown functional assays in human primary erythroid cultures and analysis of the erythroid lineage in Asf1b knockout mice, we provide evidence that ASF1B is a novel contributor to steady-state erythroid differentiation, and while its loss affects the balance of globin expression, it has no major role in hemoglobin switching. BioMed Central 2020-10-16 /pmc/articles/PMC7566067/ /pubmed/33066815 http://dx.doi.org/10.1186/s40246-020-00283-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Papadopoulos, Petros
Kafasi, Athanassia
De Cuyper, Iris M.
Barroca, Vilma
Lewandowski, Daniel
Kadri, Zahra
Veldthuis, Martijn
Berghuis, Jeffrey
Gillemans, Nynke
Cuesta, Celina María Benavente
Grosveld, Frank G.
van Zwieten, Rob
Philipsen, Sjaak
Vernet, Muriel
Gutiérrez, Laura
Patrinos, George P.
Mild dyserythropoiesis and β-like globin gene expression imbalance due to the loss of histone chaperone ASF1B
title Mild dyserythropoiesis and β-like globin gene expression imbalance due to the loss of histone chaperone ASF1B
title_full Mild dyserythropoiesis and β-like globin gene expression imbalance due to the loss of histone chaperone ASF1B
title_fullStr Mild dyserythropoiesis and β-like globin gene expression imbalance due to the loss of histone chaperone ASF1B
title_full_unstemmed Mild dyserythropoiesis and β-like globin gene expression imbalance due to the loss of histone chaperone ASF1B
title_short Mild dyserythropoiesis and β-like globin gene expression imbalance due to the loss of histone chaperone ASF1B
title_sort mild dyserythropoiesis and β-like globin gene expression imbalance due to the loss of histone chaperone asf1b
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566067/
https://www.ncbi.nlm.nih.gov/pubmed/33066815
http://dx.doi.org/10.1186/s40246-020-00283-3
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