| Autor: |
Ferguson, Chloe A., Firulli, Beth A., Zoia, Matteo, Osterwalder, Marco, Firulli, Anthony B. |
| Předmět: |
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| Zdroj: |
Developmental Dynamics; Feb2024, Vol. 253 Issue 2, p215-232, 18p |
| Abstrakt: |
Background: The 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. Results: Remarkably, 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. Conclusions: Together, these results start to uncover the diverse regulatory potential inherent to the Hand2 upstream regulatory interval. Key Findings: Identification of two independent transcriptional enhancers for Hand2The ‐106kb enhancer expresses specifically with the smooth muscle and enteric neurons of the embryonic stomachThe ‐186kb enhancer expresses with the developing limbs in a pattern that is inconsistent with Hand2 gene expression. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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