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A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8
Akiko Nakanishi1, Naoki Kobayashi, Asuka Suzuki-Hirano
1Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa, Japan.
Plos One
|September 1, 2012
Summary
Short interspersed repetitive elements (SINEs) can act as enhancers. A novel SINE locus, AS071, drives fibroblast growth factor 8 (Fgf8) expression in the developing brain, revealing modular enhancer organization.
Area of Science:
- Genomics
- Developmental Biology
- Evolutionary Biology
Background:
- Transposable elements, including short interspersed repetitive elements (SINEs), constitute a significant portion of mammalian genomes.
- These elements are crucial sources of conserved non-coding elements (CNEs) involved in gene regulation and species diversification.
- AmnSINE1, a novel SINE family, includes mammalian-specific CNEs, with one locus (AS071) showing enhancer activity in the developing diencephalon.
Purpose of the Study:
- To investigate the enhancer property of the AmnSINE1 locus AS071 in the developing mouse diencephalon.
- To determine if AS071 directs the expression of fibroblast growth factor 8 (Fgf8).
- To elucidate the functional organization and regulatory mechanisms of the AS071 enhancer.
Main Methods:
- Generation of three independent lines of AS071-transgenic mice.
- Expression profiling of AS071-driven lacZ and Fgf8 across embryonic stages.
- Enhancer assays using constructs with partially deleted AS071 sequences.
Main Results:
- AS071 functions as a distal enhancer, directing Fgf8 expression in the developing diencephalon.
- AS071 exhibits a modular organization with at least three distinct sub-elements.
- These sub-elements cooperatively regulate enhancer activity in specific diencephalic domains, including the ventral hypothalamus via an AmnSINE1-derived element.
Conclusions:
- AS071 is a distal enhancer that precisely controls Fgf8 expression in the developing diencephalon.
- The study reveals a novel modular enhancer structure with sub-elements conferring regional specificity.
- This finding advances understanding of retroposon-derived regulatory elements and enhancer domain-specificity determination.
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