ArticleDevelopmental dynamics : an official publication of the American Association of Anatomists2024
Identification and characterization of Hand2 upstream genomic enhancers active in developing stomach and limbs.
Article in Developmental dynamics : an official publication of the American Association of Anatomists, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 5 citations in OpenAlex.
- Lineage labeling with zebrafish hand2 Cre and CreERT2 recombinase CRISPR knock-ins.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Article
- Non-invasive colorectal cancer biomarkers: HAND2 and GPM6A methylation in circulating tumour DNA.Cancer cell international · 2025Article
- Lineage labeling with zebrafishbioRxiv : the preprint server for biology · 2024Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe bHLH transcription factor HAND2 plays important roles in the development of the embryonic heart, face, limbs, and sympathetic and enteric nervous systems. To define how and when HAND2 regulates these developmental systems, requires understanding the transcriptional regulation of Hand2.
resultsRemarkably, Hand2 is flanked by an extensive upstream gene desert containing a potentially diverse enhancer landscape. Here, we screened the regulatory interval 200 kb proximal to Hand2 for putative enhancers using evolutionary conservation and histone marks in Hand2-expressing tissues. H3K27ac signatures across embryonic tissues pointed to only two putative enhancer regions showing deep sequence conservation. Assessment of the transcriptional enhancer potential of these elements using transgenic reporter lines uncovered distinct in vivo enhancer activities in embryonic stomach and limb mesenchyme, respectively. Activity of the identified stomach enhancer was restricted to the developing antrum and showed expression within the smooth muscle and enteric neurons. Surprisingly, the activity pattern of the limb enhancer did not overlap Hand2 mRNA but consistently yielded a defined subectodermal anterior expression pattern within multiple transgenic lines.
conclusionsTogether, these results start to uncover the diverse regulatory potential inherent to the Hand2 upstream regulatory interval.
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