The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis.
Hematopoiesis is precisely orchestrated by lineage-specific DNA-binding proteins that regulate transcription in concert with coactivators and corepressors. Mutations in the zebrafish moonshine (mon) gene specifically disrupt both embryonic and adult hematopoiesis, resulting in severe red blood cell...
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Public Library of Science (PLoS)
2004-08-01
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Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0020237&type=printable |
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author | David G Ransom Nathan Bahary Knut Niss David Traver Caroline Burns Nikolaus S Trede Noelle Paffett-Lugassy Walter J Saganic C Anthoney Lim Candace Hersey Yi Zhou Bruce A Barut Shuo Lin Paul D Kingsley James Palis Stuart H Orkin Leonard I Zon |
author_facet | David G Ransom Nathan Bahary Knut Niss David Traver Caroline Burns Nikolaus S Trede Noelle Paffett-Lugassy Walter J Saganic C Anthoney Lim Candace Hersey Yi Zhou Bruce A Barut Shuo Lin Paul D Kingsley James Palis Stuart H Orkin Leonard I Zon |
author_sort | David G Ransom |
collection | DOAJ |
description | Hematopoiesis is precisely orchestrated by lineage-specific DNA-binding proteins that regulate transcription in concert with coactivators and corepressors. Mutations in the zebrafish moonshine (mon) gene specifically disrupt both embryonic and adult hematopoiesis, resulting in severe red blood cell aplasia. We report that mon encodes the zebrafish ortholog of mammalian transcriptional intermediary factor 1gamma (TIF1gamma) (or TRIM33), a member of the TIF1 family of coactivators and corepressors. During development, hematopoietic progenitor cells in mon mutants fail to express normal levels of hematopoietic transcription factors, including gata1, and undergo apoptosis. Three different mon mutant alleles each encode premature stop codons, and enforced expression of wild-type tif1gamma mRNA rescues embryonic hematopoiesis in homozygous mon mutants. Surprisingly, a high level of zygotic tif1gamma mRNA expression delineates ventral mesoderm during hematopoietic stem cell and progenitor formation prior to gata1 expression. Transplantation studies reveal that tif1gamma functions in a cell-autonomous manner during the differentiation of erythroid precursors. Studies in murine erythroid cell lines demonstrate that Tif1gamma protein is localized within novel nuclear foci, and expression decreases during erythroid cell maturation. Our results establish a major role for this transcriptional intermediary factor in the differentiation of hematopoietic cells in vertebrates. |
format | Article |
id | doaj-art-409d4c8fde6f4b679fcb4de597e44cca |
institution | Kabale University |
issn | 1544-9173 1545-7885 |
language | English |
publishDate | 2004-08-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS Biology |
spelling | doaj-art-409d4c8fde6f4b679fcb4de597e44cca2025-02-12T05:30:23ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852004-08-0128E23710.1371/journal.pbio.0020237The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis.David G RansomNathan BaharyKnut NissDavid TraverCaroline BurnsNikolaus S TredeNoelle Paffett-LugassyWalter J SaganicC Anthoney LimCandace HerseyYi ZhouBruce A BarutShuo LinPaul D KingsleyJames PalisStuart H OrkinLeonard I ZonHematopoiesis is precisely orchestrated by lineage-specific DNA-binding proteins that regulate transcription in concert with coactivators and corepressors. Mutations in the zebrafish moonshine (mon) gene specifically disrupt both embryonic and adult hematopoiesis, resulting in severe red blood cell aplasia. We report that mon encodes the zebrafish ortholog of mammalian transcriptional intermediary factor 1gamma (TIF1gamma) (or TRIM33), a member of the TIF1 family of coactivators and corepressors. During development, hematopoietic progenitor cells in mon mutants fail to express normal levels of hematopoietic transcription factors, including gata1, and undergo apoptosis. Three different mon mutant alleles each encode premature stop codons, and enforced expression of wild-type tif1gamma mRNA rescues embryonic hematopoiesis in homozygous mon mutants. Surprisingly, a high level of zygotic tif1gamma mRNA expression delineates ventral mesoderm during hematopoietic stem cell and progenitor formation prior to gata1 expression. Transplantation studies reveal that tif1gamma functions in a cell-autonomous manner during the differentiation of erythroid precursors. Studies in murine erythroid cell lines demonstrate that Tif1gamma protein is localized within novel nuclear foci, and expression decreases during erythroid cell maturation. Our results establish a major role for this transcriptional intermediary factor in the differentiation of hematopoietic cells in vertebrates.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0020237&type=printable |
spellingShingle | David G Ransom Nathan Bahary Knut Niss David Traver Caroline Burns Nikolaus S Trede Noelle Paffett-Lugassy Walter J Saganic C Anthoney Lim Candace Hersey Yi Zhou Bruce A Barut Shuo Lin Paul D Kingsley James Palis Stuart H Orkin Leonard I Zon The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis. PLoS Biology |
title | The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis. |
title_full | The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis. |
title_fullStr | The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis. |
title_full_unstemmed | The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis. |
title_short | The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis. |
title_sort | zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma an essential regulator of hematopoiesis |
url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0020237&type=printable |
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