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A Cdx4-Sall4 Regulatory Module Controls the Transition from Mesoderm Formation to Embryonic Hematopoiesis
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-s...
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Published in: | Stem cell reports 2013-11, Vol.1 (5), p.425-436 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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.
•Cdx4 and Sall4 bind to each other’s genomic loci•Cdx4 and Sall4 coregulate genes responsible for the mesoderm-to-blood transition•Scl and Lmo2 overexpression rescues blood defects in cdx4/sall4 double morphants
By utilizing chromatin immunoprecipitation sequencing combined with gene-expression profiling in zebrafish, Zon and colleagues demonstrate a Cdx4-Sall4 regulatory module that is crucial for the mesoderm-to-blood transition during embryogenesis. Their model suggests that Cdx4 and Sall4 cross-regulate each other and directly control hox genes and the hematopoietic transcription factors Scl (TAL1) and Lmo2, further moving the mesoderm toward a blood lineage. |
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ISSN: | 2213-6711 2213-6711 |
DOI: | 10.1016/j.stemcr.2013.10.001 |