Authors: | Paik, E. J.; Mahony, S.; White, R. M.; Price, E. N.; Dibiase, A.; Dorjsuren, B.; Mosimann, C.; Davidson, A. J.; Gifford, D.; Zon, L. I. |
Article Title: | A Cdx4-sall4 regulatory module controls the transition from mesoderm formation to embryonic hematopoiesis |
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. © 2013 The Authors. |
Keywords: | gene mutation; nonhuman; gene; gene targeting; gene overexpression; gene expression profiling; erythropoiesis; embryo; animal experiment; gene locus; transcription factor; regulatory mechanism; microarray analysis; cell transformation; chromatin immunoprecipitation; hematopoiesis; erythrocyte; gene silencing; mesoderm; zebra fish; danio rerio; transcription factor gata 1; autoregulation; lmo2 gene; hox gene; somite; scl gene; priority journal; article; transcription factor cdx1; cross regulation; transcription factor cdx1a gene; transcription factor cdx4 gene; transcription factor spalt like 4 gene |
Journal Title: | Stem Cell Reports |
Volume: | 1 |
Issue: | 5 |
ISSN: | 2213-6711 |
Publisher: | Cell Press |
Date Published: | 2013-11-07 |
Start Page: | 425 |
End Page: | 436 |
Language: | English |
DOI: | 10.1016/j.stemcr.2013.10.001 |
PROVIDER: | scopus |
PMCID: | PMC3841246 |
PUBMED: | 24286030 |
DOI/URL: | |
Notes: | Export Date: 2 January 2014 -- Source: Scopus |