An integrated functional genomics approach reveals novel functions of three conserved T-box transcription factors in zebrafish germlayer formation

11/12/2012 - Room C209 at 14:00 - External Seminar
Dr Andrew Nelson
(Sir William Dunn School of Pathology)
The Nodal signalling pathway participates in a number of key processes in early vertebrate development, including mesoderm and endoderm formation. It functions through receptor activation of the transcription factors Smad2/3, which migrate to the nucleus and interact with other transcription factors to regulate Nodal target genes. Whilst an increasing number of factors which interact with Smad2/3 are being identified, how they partition the Nodal signal is not well understood. One such interacting factor is the T-box transcription factor, Eomesodermin (Eomesa). In order to study the role of Eomesa in mediating the Nodal signal we performed ChIP-seq for Smad2 and Eomesa, and correlated their genomic binding profiles with Nodal- and Eomesa-responsive genes. Our findings indicate a role for Eomesa in both mesoderm and endoderm formation. Two other T-box factors, No tail (Ntla) and T-box gene 16 (Tbx16), are induced by Nodal and have well-established roles in mesoderm formation. These factors share many target genes and in three cases are known to act through the same enhancers. In order to further study their functional relationship we performed ChIP-seq for both factors and compared the data to microarray profiles of their individual and combinatorial perturbation. Our analyses reveal widespread redundancy of the two factors in regulating their target genes. The consequent genetic interaction manifests as a surprising phenotype, revealing a novel function of Ntla and Tbx16.
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