scholarly journals Discovery of genes required for body axis and limb formation by global identification of retinoic acid–regulated epigenetic marks

PLoS Biology ◽  
2020 ◽  
Vol 18 (5) ◽  
pp. e3000719 ◽  
Author(s):  
Marie Berenguer ◽  
Karolin F. Meyer ◽  
Jun Yin ◽  
Gregg Duester
2019 ◽  
Author(s):  
Marie Berenguer ◽  
Karolin F. Meyer ◽  
Jun Yin ◽  
Gregg Duester

AbstractIdentification of target genes that mediate required functions downstream of transcription factors is hampered by the large number of genes whose expression changes when the factor is removed from a specific tissue and the numerous binding sites for the factor in the genome. Retinoic acid (RA) regulates transcription via RA receptors bound to RA response elements (RAREs) of which there are thousands in vertebrate genomes. Here, we combined ChIP-seq for epigenetic marks and RNA-seq on trunk tissue from wild-type and Aldh1a2-/-embryos lacking RA synthesis that exhibit body axis and forelimb defects. We identified a relatively small number of genes with altered expression when RA is missing that also have nearby RA-regulated deposition of H3K27ac (gene activation mark) or H3K27me3 (gene repression mark) associated with conserved RAREs, suggesting they have important downstream functions. RA-regulated epigenetic marks were identified near RA target genes already known to be required for body axis and limb formation, thus validating our approach, plus many other candidate RA target genes were found. Nr2f1, Nr2f2, Meis1, and Meis2 gene family members were identified by our approach, and double knockouts of each family demonstrated previously unknown requirements for body axis and/or limb formation. These findings demonstrate that our method for identifying RA-regulated epigenetic marks can be used to discover genes important for development.


Development ◽  
2014 ◽  
Vol 141 (15) ◽  
pp. 2972-2977 ◽  
Author(s):  
S. Kumar ◽  
G. Duester

genesis ◽  
2011 ◽  
Vol 49 (10) ◽  
pp. 776-783 ◽  
Author(s):  
Thomas J. Cunningham ◽  
Xianling Zhao ◽  
Gregg Duester

2018 ◽  
Vol 441 (1) ◽  
pp. 127-131 ◽  
Author(s):  
Marie Berenguer ◽  
Joseph J. Lancman ◽  
Thomas J. Cunningham ◽  
P. Duc Si Dong ◽  
Gregg Duester

BioEssays ◽  
1990 ◽  
Vol 12 (9) ◽  
pp. 437-439 ◽  
Author(s):  
Jeremy B. A. Green
Keyword(s):  

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Filomena Caccavale ◽  
Giovanni Annona ◽  
Lucie Subirana ◽  
Hector Escriva ◽  
Stephanie Bertrand ◽  
...  

During animal ontogenesis, body axis patterning is finely regulated by complex interactions among several signaling pathways. Nitric oxide (NO) and retinoic acid (RA) are potent morphogens that play a pivotal role in vertebrate development. Their involvement in axial patterning of the head and pharynx shows conserved features in the chordate phylum. Indeed, in the cephalochordate amphioxus, NO and RA are crucial for the correct development of pharyngeal structures. Here, we demonstrate the functional cooperation between NO and RA that occurs during amphioxus embryogenesis. During neurulation, NO modulates RA production through the transcriptional regulation of Aldh1a.2 that irreversibly converts retinaldehyde into RA. On the other hand, RA directly or indirectly regulates the transcription of Nos genes. This reciprocal regulation of NO and RA pathways is essential for the normal pharyngeal development in amphioxus and it could be conserved in vertebrates.


2009 ◽  
Vol 19 (12) ◽  
pp. 1050-1057 ◽  
Author(s):  
Xianling Zhao ◽  
Ioan Ovidiu Sirbu ◽  
Felix A. Mic ◽  
Natalia Molotkova ◽  
Andrei Molotkov ◽  
...  

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