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PMID:24445282

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Citation

Hu, B, Zhang, W, Feng, X, Ji, W, Xie, X and Xiao, W' (2014) Zebrafish eaf1 suppresses foxo3b expression to modulate transcriptional activity of gata1 and spi1 in primitive hematopoiesis. Dev. Biol. '

Abstract

Studies implicate a potential role for EAF1 in MLL-ELL induced leukemogenesis; however the biological function of EAF1 in this process remains unknown. In this study, we show that knockdown of zebrafish eaf1 by morpholinos caused serious defects in both primitive and definitive hematopoiesis. Using microarray analysis, we identified foxo3b as a target gene suppressed by eaf1. Ectopic expression of foxo3b in embryos mimicked the phenotypes exhibited in eaf1 morphants, except that foxo3b had no effect on runx1 and c-myb expression while eaf1 morphants did not express these markers in the ventral wall of dorsal aorta. Subsequent experiments showed that a dominant negative form of foxo3b (dn-foxo3b) partially restored primitive hematopoietic defects in eaf1 morphants, suggesting that foxo3b might serve as a key factor for mediating eaf1 function in primitive hematopoiesis. Furthermore, we observed that foxo3b inhibited the transcriptional activity of gata1 and spi1 through protein-protein interaction. Our findings not only suggest a function of eaf1 on hematopoiesis in vivo, but also reveal a novel regulatory pathway, eaf1-foxo3b-gata1/spi1, that may shed light on the role of EAF1 in MLL-ELL induced leukemogenesis.

Links

PubMed Online version:10.1016/j.ydbio.2014.01.005

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:B3DGQ4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-980526-268

F

Seeded From UniProt

complete

DANRE:B3DGQ4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-980526-164

F

Seeded From UniProt

complete

DANRE:B3DGQ4

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:B3DGQ4

involved_in

GO:0060215: primitive hemopoiesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENE-040625-109

P

Seeded From UniProt

complete

DANRE:E9QHY6

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:E9QHY6

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:E9QHY6

involved_in

GO:0060216: definitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-130501-8

P

Seeded From UniProt

complete

DANRE:E9QHY6

involved_in

GO:0060215: primitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-130501-8

P

Seeded From UniProt

complete

DANRE:E9QHY6

involved_in

GO:0060215: primitive hemopoiesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

P

Seeded From UniProt

complete

DANRE:F1R668

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

F

Seeded From UniProt

complete

DANRE:Q05AJ3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

F

Seeded From UniProt

complete

DANRE:Q5TYS1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-980526-268

F

Seeded From UniProt

complete

DANRE:Q5TYS1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-980526-164

F

Seeded From UniProt

complete

DANRE:Q5TYS1

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q5TYS1

involved_in

GO:0060215: primitive hemopoiesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENE-040625-109

P

Seeded From UniProt

complete

DANRE:Q6IQD2

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q6IQD2

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:Q6IQD2

involved_in

GO:0060216: definitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-130501-8

P

Seeded From UniProt

complete

DANRE:Q6IQD2

involved_in

GO:0060215: primitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-130501-8

P

Seeded From UniProt

complete

DANRE:Q6IQD2

involved_in

GO:0060215: primitive hemopoiesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

P

Seeded From UniProt

complete

DANRE:Q6PHV7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

F

Seeded From UniProt

complete

DANRE:Q6WEE0

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

F

Seeded From UniProt

complete

DANRE:Q6WEE1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

F

Seeded From UniProt

complete

DANRE:Q78AM8

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

F

Seeded From UniProt

complete

DANRE:Q8AW41

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

F

Seeded From UniProt

complete

DANRE:Q8JID4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

F

Seeded From UniProt

complete

DANRE:Q90410

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-990708-6

F

Seeded From UniProt

complete

DANRE:Q9PVK6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-980526-268

F

Seeded From UniProt

complete

DANRE:Q9PVK6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-980526-164

F

Seeded From UniProt

complete

DANRE:Q9PVK6

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q9PVK6

involved_in

GO:0060215: primitive hemopoiesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENE-040625-109

P

Seeded From UniProt

complete

DANRE:Q9W7F8

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-980526-268

F

Seeded From UniProt

complete

DANRE:Q9W7F8

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

ZFIN:ZDB-GENE-980526-164

F

Seeded From UniProt

complete

DANRE:Q9W7F8

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q9W7F8

involved_in

GO:0060215: primitive hemopoiesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENE-040625-109

P

Seeded From UniProt

complete

HUMAN:EAF1

GO:0030097: hemopoiesis

ECO:0000314:

P

Figure 1. Eaf1 promotes hematopoiesis.

complete
CACAO 9232

HUMAN:EAF1

GO:0010629: negative regulation of gene expression

ECO:0000314:

P

Figure 3. Eaf1 suppresses human FOXO 3a expression.

complete
CACAO 9267

See also

References

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