Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2009-12-16
pubmed:abstractText
The transcription factor Gata1 is required for the development of erythrocytes and megakaryocytes. Previous studies with a complementation rescue approach showed that the zinc finger domains are required for both primitive and definitive hematopoiesis. Here we report a novel zebrafish gata1 mutant with an N-ethyl-N-nitrosourea-induced point mutation in the C-finger (gata1(T301K)). The Gata1 protein with this mutation bound to its DNA target sequence with reduced affinity and transactivated inefficiently in a reporter assay. gata1(T301K/T301K) fish had a decreased number of erythrocytes during primitive hematopoiesis but normal adult hematopoiesis. We crossed the gata1(T301K/T301K) fish with those carrying the R339X mutation, also known as vlad tepes (vlt), which abolishes DNA binding and transactivation activities. As we reported previously, gata1(vlt/vlt) embryos were "bloodless" and died approximately 11 to 15 days after fertilization. Interestingly, the gata1(T301K/vlt) fish had nearly a complete block of primitive hematopoiesis, but they resumed hematopoiesis between 7 and 14 days after fertilization and grew to phenotypically normal fish with normal adult hematopoiesis. Our findings suggest that the impact of Gata1 on hematopoiesis correlates with its DNA-binding ability and that primitive hematopoiesis is more sensitive to reduction in Gata1 function than definitive hematopoiesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5162-72
pubmed:dateRevised
2011-10-7
pubmed:meshHeading
pubmed-meshheading:19843882-Amino Acid Sequence, pubmed-meshheading:19843882-Animals, pubmed-meshheading:19843882-Binding Sites, pubmed-meshheading:19843882-DNA, pubmed-meshheading:19843882-Embryo, Nonmammalian, pubmed-meshheading:19843882-Female, pubmed-meshheading:19843882-Flow Cytometry, pubmed-meshheading:19843882-GATA1 Transcription Factor, pubmed-meshheading:19843882-Gene Expression Regulation, Developmental, pubmed-meshheading:19843882-Hematopoiesis, pubmed-meshheading:19843882-In Situ Hybridization, pubmed-meshheading:19843882-Male, pubmed-meshheading:19843882-Models, Molecular, pubmed-meshheading:19843882-Molecular Sequence Data, pubmed-meshheading:19843882-Mutation, pubmed-meshheading:19843882-Nucleic Acid Conformation, pubmed-meshheading:19843882-Protein Binding, pubmed-meshheading:19843882-Protein Structure, Tertiary, pubmed-meshheading:19843882-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19843882-Sequence Homology, Amino Acid, pubmed-meshheading:19843882-Transcriptional Activation, pubmed-meshheading:19843882-Zebrafish, pubmed-meshheading:19843882-Zebrafish Proteins
pubmed:year
2009
pubmed:articleTitle
Differential requirement for Gata1 DNA binding and transactivation between primitive and definitive stages of hematopoiesis in zebrafish.
pubmed:affiliation
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Intramural