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Trompouki, Eirini

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Trompouki

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Eirini

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Trompouki, Eirini

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20122

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Author's Publications: search.filters.isAuthorOfPublication.81202796-3ea4-4f75-ba66-6aa633daff24

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    Zebrafish Globin Switching Occurs in Two Developmental Stages and Is Controlled by the LCR
    (Elsevier BV, 2012) Ganis, Jared Jason; Hsia, Nelson; Trompouki, Eirini; de Jong, Jill L.O.; DiBiase, Anthony; Lambert, Janelle S.; Jia, Zhiying; Sabo, Peter J.; Weaver, Molly; Sandstrom, Richard; Stamatoyannopoulos, John A.; Zhou, Yi; Zon, Leonard
    Globin gene switching is a complex, highly regulated process allowing expression of distinct globin genes at specific developmental stages. Here, for the first time, we have characterized all of the zebrafish globins based on the completed genomic sequence. Two distinct chromosomal loci, termed major (chromosome 3) and minor (chromosome 12), harbor the globin genes containing α/β pairs in a 5′–3′ to 3′–5′ orientation. Both these loci share synteny with the mammalian α-globin locus. Zebrafish globin expression was assayed during development and demonstrated two globin switches, similar to human development. A conserved regulatory element, the locus control region (LCR), was revealed by analyzing DNase I hypersensitive sites, H3K4 trimethylation marks and GATA1 binding sites. Surprisingly, the position of these sites with relation to the globin genes is evolutionarily conserved, despite a lack of overall sequence conservation. Motifs within the zebrafish LCR include CACCC, GATA, and NFE2 sites, suggesting functional interactions with known transcription factors but not the same LCR architecture. Functional homology to the mammalian α-LCR MCS-R2 region was confirmed by robust and specific reporter expression in erythrocytes of transgenic zebrafish. Our studies provide a comprehensive characterization of the zebrafish globin loci and clarify the regulation of globin switching.
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    Nanog-like Regulates Endoderm Formation through the Mxtx2-Nodal Pathway
    (Elsevier, 2012) Xu, Cong; Fan, Zi Peng; Müller, Patrick; Fogley, Rachel; DiBiase, Anthony; Trompouki, Eirini; Unternaehrer, Juli; Xiong, Fengzhu; Torregroza, Ingrid; Evans, Todd; Megason, Sean; Daley, George; Schier, Alexander; Young, Richard A.; Zon, Leonard
    In mammalian embryonic stem cells, the acquisition of pluripotency is dependent on Nanog, but the in vivo analysis of Nanog has been hampered by its requirement for early mouse development. In an effort to examine the role of Nanog in vivo, we identi- fied a zebrafish Nanog ortholog and found that its knockdown impaired endoderm formation. Genome-wide transcription analysis revealed that nanog-like morphants fail to develop the extraembry- onic yolk syncytial layer (YSL), which produces Nodal, required for endoderm induction. We exam- ined the genes that were regulated by Nanog-like and identified the homeobox gene mxtx2, which is both necessary and sufficient for YSL induction. Chromatin immunoprecipitation assays and genetic studies indicated that Nanog-like directly activates mxtx2, which, in turn, specifies the YSL lineage by directly activating YSL genes. Our study identifies a Nanog-like-Mxtx2-Nodal pathway and establishes a role for Nanog-like in regulating the formation of the extraembryonic tissue required for endoderm induction.