Title

Initiation of zebrafish haematopoiesis by the TATA-box-binding protein-related factor Trf3

UMMS Affiliation

Program in Molecular Medicine; Program in Gene Function and Expression Program in Gene Function and Expression

Date

11-30-2007

Document Type

Article

Subjects

Animals; Basic Helix-Loop-Helix Transcription; Factors; Embryonic Development; Gene Expression Profiling; Gene Expression Regulation, Developmental; *Hematopoiesis; Homeodomain Proteins; Mice; TATA Box Binding Protein-Like Proteins; Zebrafish; Zebrafish Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

TATA-box-binding protein (TBP)-related factor 3, TRF3 (also called TBP2), is a vertebrate-specific member of the TBP family that has a conserved carboxy-terminal region and DNA-binding domain virtually identical to that of TBP (ref. 1). TRF3 is highly expressed during embryonic development, and studies in zebrafish and Xenopus have shown that it is required for normal embryogenesis. Here we show that zebrafish embryos depleted of Trf3 exhibit multiple developmental defects and, in particular, fail to undergo haematopoiesis. Expression profiling for Trf3-dependent genes identified mespa, which encodes a transcription factor whose murine orthologue is required for mesoderm specification, and chromatin immunoprecipitation verified that Trf3 binds to the mespa promoter. Depletion of Mespa resulted in developmental and haematopoietic defects markedly similar to those induced by Trf3 depletion. Injection of mespa messenger RNA (mRNA) restored normal development to a Trf3-depleted embryo, indicating mespa is the single Trf3 target gene required for zebrafish embryogenesis. Zebrafish embryos depleted of Trf3 or Mespa also failed to express cdx4, a caudal-related gene required for haematopoiesis. Mespa binds to the cdx4 promoter, and epistasis analysis revealed an ordered trf3-mespa-cdx4 pathway. Thus, in zebrafish, commitment of mesoderm to the haematopoietic lineage occurs through a transcription factor pathway initiated by a TBP-related factor.

Rights and Permissions

Citation: Nature. 2007 Dec 13;450(7172):1082-5. Epub 2007 Nov 28. Link to article on publisher's site

DOI of Published Version

10.1038/nature06349

Related Resources

Link to Article in PubMed

Journal Title

Nature

PubMed ID

18046332