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rdf:type |
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lifeskim:mentions |
umls-concept:C0007589,
umls-concept:C0008546,
umls-concept:C0038250,
umls-concept:C0086418,
umls-concept:C0086860,
umls-concept:C0205177,
umls-concept:C0205225,
umls-concept:C0332281,
umls-concept:C1511938,
umls-concept:C1516960,
umls-concept:C1708936
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pubmed:issue |
9
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pubmed:dateCreated |
2009-9-16
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pubmed:abstractText |
Growth Factor Independent-1B (Gfi-1B) is a transcriptional repressor that plays critical roles in the control of erythropoiesis and megakaryopoiesis. Gfi-1B expression was described to be repressed by an autoregulatory feedback control loop. Here, we show that Gfi-1 transcription is positively regulated early after induction of erythroid differentiation and remains highly active to late erythroblasts. Using chromatin immunoprecipitation assays in CD34+ cells from human cord blood, we found that Gfi-1 and GATA-2 in immature progenitors and then Gfi-1B and GATA-1 in erythroblasts are bound to the Gfi-1B promoter as well as to the promoter of c-myc, a known Gfi-1B target gene. Surprisingly, this Gfi-1/GATA-2-Gfi-1B/GATA-1 switch observed at erythroblast stages is associated to an increase in the Gfi-1B transcription whereas it triggers repression of c-myc transcription. Accordingly, analysis of chromatin modification patterns shows that HDAC, CoREST, and LSD1 are recruited to the c-myc promoter leading to appearance of repressive chromatin marks. In contrast, the Gfi-1B promoter remains associated with a transcriptionally active chromatin configuration as highlighted by an increase in histone H3 acetylation and concomitant release of the LSD1 and CoREST corepressors. The repressive function of Gfi-1B therefore depends on the nature of the proteins recruited to the target gene promoters and on chromatin modifications. We conclude that Gfi-1B behaves as a lineage-affiliated gene with an open chromatin configuration in multipotent progenitors and sustained activation as cells progress throughout erythroid differentiation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/GATA1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GATA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GATA2 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GFI1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Demethylases,
http://linkedlifedata.com/resource/pubmed/chemical/KDM1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/MYC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/RCOR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1549-4918
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2153-62
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pubmed:dateRevised |
2011-10-27
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pubmed:meshHeading |
pubmed-meshheading:19522008-Blotting, Western,
pubmed-meshheading:19522008-Cell Differentiation,
pubmed-meshheading:19522008-Cell Line,
pubmed-meshheading:19522008-Chromatin,
pubmed-meshheading:19522008-Chromatin Immunoprecipitation,
pubmed-meshheading:19522008-Erythroid Cells,
pubmed-meshheading:19522008-GATA1 Transcription Factor,
pubmed-meshheading:19522008-GATA2 Transcription Factor,
pubmed-meshheading:19522008-Genetic Vectors,
pubmed-meshheading:19522008-Histone Demethylases,
pubmed-meshheading:19522008-Humans,
pubmed-meshheading:19522008-Lentivirus,
pubmed-meshheading:19522008-Nerve Tissue Proteins,
pubmed-meshheading:19522008-Polymerase Chain Reaction,
pubmed-meshheading:19522008-Promoter Regions, Genetic,
pubmed-meshheading:19522008-Protein Binding,
pubmed-meshheading:19522008-Proto-Oncogene Proteins,
pubmed-meshheading:19522008-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:19522008-Repressor Proteins,
pubmed-meshheading:19522008-Transfection
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pubmed:year |
2009
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pubmed:articleTitle |
Gfi-1B promoter remains associated with active chromatin marks throughout erythroid differentiation of human primary progenitor cells.
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pubmed:affiliation |
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (UMR 8104), Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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