BACKGROUND: In erythroblasts, the CoREST repressor complex is recruited to target promoters by the transcription factor Gfi1b, leading to repression of genes mainly involved in erythroid differentiation. Hmg20b is a subunit of CoREST, but its role in erythropoiesis has not yet been established. DESIGN AND METHODS: To study the role of Hmg20b in erythropoiesis, we performed knockdown experiments in a differentiation-competent mouse fetal liver cell line, and in primary mouse fetal liver cells. The effects on globin gene expression were determined. We used microarrays to investigate global gene expression changes induced by Hmg20b knockdown. Functional analysis was carried out on Hrasls3, an Hmg20b target gene. RESULTS: We show that Hmg20b depletion induces spontaneous differentiation. To identify the target genes of Hmg20b, microarray analysis was performed on Hmg20b knockdown cells and controls. In line with its association to the CoREST complex, we found that 85% (527 out of 620) of the deregulated genes are up-regulated when Hmg20b levels are reduced. Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation. Among the consistently up-regulated targets were embryonic β-like globins and the phospholipase HRAS-like suppressor 3 (Hrasls3). We show that Hrasls3 expression is induced during erythroid differentiation and that knockdown of Hrasls3 inhibits terminal differentiation of proerythroblasts. CONCLUSIONS: We conclude that Hmg20b acts as an inhibitor of erythroid differentiation, through the down-regulation of genes involved in differentiation such as Hrasls3, and activation of repressors of differentiation such as Gfi1b. In addition, Hmg20b suppresses embryonic β-like globins.
BACKGROUND: In erythroblasts, the CoREST repressor complex is recruited to target promoters by the transcription factor Gfi1b, leading to repression of genes mainly involved in erythroid differentiation. Hmg20b is a subunit of CoREST, but its role in erythropoiesis has not yet been established. DESIGN AND METHODS: To study the role of Hmg20b in erythropoiesis, we performed knockdown experiments in a differentiation-competent mouse fetal liver cell line, and in primary mouse fetal liver cells. The effects on globin gene expression were determined. We used microarrays to investigate global gene expression changes induced by Hmg20b knockdown. Functional analysis was carried out on Hrasls3, an Hmg20b target gene. RESULTS: We show that Hmg20b depletion induces spontaneous differentiation. To identify the target genes of Hmg20b, microarray analysis was performed on Hmg20b knockdown cells and controls. In line with its association to the CoREST complex, we found that 85% (527 out of 620) of the deregulated genes are up-regulated when Hmg20b levels are reduced. Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation. Among the consistently up-regulated targets were embryonic β-like globins and the phospholipase HRAS-like suppressor 3 (Hrasls3). We show that Hrasls3 expression is induced during erythroid differentiation and that knockdown of Hrasls3 inhibits terminal differentiation of proerythroblasts. CONCLUSIONS: We conclude that Hmg20b acts as an inhibitor of erythroid differentiation, through the down-regulation of genes involved in differentiation such as Hrasls3, and activation of repressors of differentiation such as Gfi1b. In addition, Hmg20b suppresses embryonic β-like globins.
Authors: M von Lindern; E M Deiner; H Dolznig; M Parren-Van Amelsvoort; M J Hayman; E W Mullner; H Beug Journal: Oncogene Date: 2001-06-21 Impact factor: 9.867
Authors: Patrick Rodriguez; Harald Braun; Katarzyna E Kolodziej; Ernie de Boer; Jennifer Campbell; Edgar Bonte; Frank Grosveld; Sjaak Philipsen; John Strouboulis Journal: Methods Mol Biol Date: 2006
Authors: Huilan Yao; Devorah C Goldman; Tamilla Nechiporuk; Sunita Kawane; Shannon K McWeeney; Jeffrey W Tyner; Guang Fan; Marc A Kerenyi; Stuart H Orkin; William H Fleming; Gail Mandel Journal: Blood Date: 2014-03-20 Impact factor: 22.113
Authors: Alba Maiques-Diaz; Luciano Nicosia; Naseer J Basma; Isabel Romero-Camarero; Francesco Camera; Gary J Spencer; Fabio M R Amaral; Fabrizio Simeoni; Bettina Wingelhofer; Andrew J K Williamson; Andrew Pierce; Anthony D Whetton; Tim C P Somervaille Journal: Oncogene Date: 2022-09-28 Impact factor: 8.756
Authors: Rupert L Mayer; Josef D Schwarzmeier; Marlene C Gerner; Andrea Bileck; Johanna C Mader; Samuel M Meier-Menches; Samuel M Gerner; Klaus G Schmetterer; Tobias Pukrop; Albrecht Reichle; Astrid Slany; Christopher Gerner Journal: Mol Cell Proteomics Date: 2017-12-01 Impact factor: 5.911
Authors: David McClellan; Mattie J Casey; Diana Bareyan; Helena Lucente; Christopher Ours; Matthew Velinder; Jason Singer; Mehraju Din Lone; Wenxiang Sun; Yunuen Coria; Clinton C Mason; Michael E Engel Journal: Mol Cell Biol Date: 2019-06-13 Impact factor: 4.272