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A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression
Leonie Alten1, Karin Schuster-Gossler, Michael P Eichenlaub
1Institute for Molecular Biology, Medizinische Hochschule Hannover, Germany.
Plos One
|October 31, 2012
Summary
We identified a novel mammalian-specific cis-regulatory module (CRM) controlling NOTO gene expression in mouse embryos. This regulatory element is crucial for node and notochord development and function.
Area of Science:
- Developmental Biology
- Genetics
- Evolutionary Biology
Background:
- Vertebrate organizer and notochord are vital for embryonic development.
- Specific cis-regulatory modules (CRMs) control gene expression in these tissues, with varying sequence conservation.
- Some CRMs are ancient, while others have evolved more recently.
Purpose of the Study:
- Identify and characterize a mammalian-specific CRM for NOTO gene expression.
- Investigate the role of this CRM in node and notochord development in mice.
- Determine the evolutionary conservation and function of this regulatory element.
Main Methods:
- Identification and characterization of a 523 bp enhancer region (NOCE) upstream the Noto promoter.
- In vivo and in vitro functional assays to test NOCE activity.
- Comparative sequence analysis in non-mammalian vertebrates.
- Transgenic assays in fish.
Main Results:
- A mammalian-specific CRM (NOCE) was identified, essential for node and notochord specific (NNC) expression of NOTO.
- NOCE was necessary and sufficient for NNC expression from the endogenous Noto locus in mice.
- Specific subregions within NOCE, including a FOXA2 binding site and a novel motif, were critical for activity in vivo.
- NOCE showed no sequence similarity in non-mammalian vertebrates and did not drive NNC expression in transgenic fish.
Conclusions:
- NOCE is a novel, mammalian-specific CRM regulating NOTO expression.
- This CRM is crucial for restricted Noto expression in the node and nascent notochord.
- NOCE plays a key role in normal node development and function, highlighting evolutionary divergence in gene regulation.
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