A Cdx4-Sall4 Regulatory Module Controls the Transition from Mesoderm Formation to Embryonic Hematopoiesis
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Paik-2013-A Cdx4-Sall4 Regulat.pdf
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Author(s)
Paik, Elizabeth J.
Mahony, Shaun
White, Richard M.
Price, Emily N.
DiBiase, Anthony
Dorjsuren, Bilguujin
Mosimann, Christian
Davidson, Alan J.
Zon, Leonard I.
Gifford, David K.
Date Issued
November 2013
Journal
Stem Cell Reports
Publisher
Elsevier
Citation
Paik, Elizabeth J., Shaun Mahony, Richard M. White, Emily N. Price, Anthony DiBiase, Bilguujin Dorjsuren, Christian Mosimann, Alan J. Davidson, David Gifford, and Leonard I. Zon. “A Cdx4-Sall4 Regulatory Module Controls the Transition from Mesoderm Formation to Embryonic Hematopoiesis.” Stem Cell Reports 1, no. 5 (November 2013): 425–436.
Version
Final published version
Abstract
Deletion of caudal/cdx genes alters hox gene expression and causes defects in posterior tissues and hematopoiesis. Yet, the defects in hox gene expression only partially explain these phenotypes. To gain deeper insight into Cdx4 function, we performed chromatin immunoprecipitation sequencing (ChIP-seq) combined with gene-expression profiling in zebrafish, and identified the transcription factor spalt-like 4 (sall4) as a Cdx4 target. ChIP-seq revealed that Sall4 bound to its own gene locus and the cdx4 locus. Expression profiling showed that Cdx4 and Sall4 coregulate genes that initiate hematopoiesis, such as hox, scl, and lmo2. Combined cdx4/sall4 gene knockdown impaired erythropoiesis, and overexpression of the Cdx4 and Sall4 target genes scl and lmo2 together rescued the erythroid program. These findings suggest that auto- and cross-regulation of Cdx4 and Sall4 establish a stable molecular circuit in the mesoderm that facilitates the activation of the blood-specific program as development proceeds.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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DOI of Published Version
https://doi.org/10.1016/j.stemcr.2013.10.001
