A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8.
Transposable elements, including short interspersed repetitive elements (SINEs), comprise nearly half the mammalian genome. Moreover, they are a major source of conserved non-coding elements (CNEs), which play important functional roles in regulating development-related genes, such as enhancing and...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3427154?pdf=render |
| _version_ | 1828750728724742144 |
|---|---|
| author | Akiko Nakanishi Naoki Kobayashi Asuka Suzuki-Hirano Hidenori Nishihara Takeshi Sasaki Mika Hirakawa Kenta Sumiyama Tomomi Shimogori Norihiro Okada |
| author_facet | Akiko Nakanishi Naoki Kobayashi Asuka Suzuki-Hirano Hidenori Nishihara Takeshi Sasaki Mika Hirakawa Kenta Sumiyama Tomomi Shimogori Norihiro Okada |
| author_sort | Akiko Nakanishi |
| collection | DOAJ |
| description | Transposable elements, including short interspersed repetitive elements (SINEs), comprise nearly half the mammalian genome. Moreover, they are a major source of conserved non-coding elements (CNEs), which play important functional roles in regulating development-related genes, such as enhancing and silencing, serving for the diversification of morphological and physiological features among species. We previously reported a novel SINE family, AmnSINE1, as part of mammalian-specific CNEs. One AmnSINE1 locus, named AS071, showed an enhancer property in the developing mouse diencephalon. Indeed, AS071 appears to recapitulate the expression of diencephalic fibroblast growth factor 8 (Fgf8). Here we established three independent lines of AS071-transgenic mice and performed detailed expression profiling of AS071-enhanced lacZ in comparison with that of Fgf8 across embryonic stages. We demonstrate that AS071 is a distal enhancer that directs Fgf8 expression in the developing diencephalon. Furthermore, enhancer assays with constructs encoding partially deleted AS071 sequence revealed a unique modular organization in which AS071 contains at least three functionally distinct sub-elements that cooperatively direct the enhancer activity in three diencephalic domains, namely the dorsal midline and the lateral wall of the diencephalon, and the ventral midline of the hypothalamus. Interestingly, the AmnSINE1-derived sub-element was found to specify the enhancer activity to the ventral midline of the hypothalamus. To our knowledge, this is the first discovery of an enhancer element that could be separated into respective sub-elements that determine regional specificity and/or the core enhancing activity. These results potentiate our understanding of the evolution of retroposon-derived cis-regulatory elements as well as the basis for future studies of the molecular mechanism underlying the determination of domain-specificity of an enhancer. |
| first_indexed | 2024-12-10T20:42:37Z |
| format | Article |
| id | doaj.art-f21f2c956f004cc3ab2cd8505383e6b3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T20:42:37Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f21f2c956f004cc3ab2cd8505383e6b32022-12-22T01:34:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4378510.1371/journal.pone.0043785A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8.Akiko NakanishiNaoki KobayashiAsuka Suzuki-HiranoHidenori NishiharaTakeshi SasakiMika HirakawaKenta SumiyamaTomomi ShimogoriNorihiro OkadaTransposable elements, including short interspersed repetitive elements (SINEs), comprise nearly half the mammalian genome. Moreover, they are a major source of conserved non-coding elements (CNEs), which play important functional roles in regulating development-related genes, such as enhancing and silencing, serving for the diversification of morphological and physiological features among species. We previously reported a novel SINE family, AmnSINE1, as part of mammalian-specific CNEs. One AmnSINE1 locus, named AS071, showed an enhancer property in the developing mouse diencephalon. Indeed, AS071 appears to recapitulate the expression of diencephalic fibroblast growth factor 8 (Fgf8). Here we established three independent lines of AS071-transgenic mice and performed detailed expression profiling of AS071-enhanced lacZ in comparison with that of Fgf8 across embryonic stages. We demonstrate that AS071 is a distal enhancer that directs Fgf8 expression in the developing diencephalon. Furthermore, enhancer assays with constructs encoding partially deleted AS071 sequence revealed a unique modular organization in which AS071 contains at least three functionally distinct sub-elements that cooperatively direct the enhancer activity in three diencephalic domains, namely the dorsal midline and the lateral wall of the diencephalon, and the ventral midline of the hypothalamus. Interestingly, the AmnSINE1-derived sub-element was found to specify the enhancer activity to the ventral midline of the hypothalamus. To our knowledge, this is the first discovery of an enhancer element that could be separated into respective sub-elements that determine regional specificity and/or the core enhancing activity. These results potentiate our understanding of the evolution of retroposon-derived cis-regulatory elements as well as the basis for future studies of the molecular mechanism underlying the determination of domain-specificity of an enhancer.http://europepmc.org/articles/PMC3427154?pdf=render |
| spellingShingle | Akiko Nakanishi Naoki Kobayashi Asuka Suzuki-Hirano Hidenori Nishihara Takeshi Sasaki Mika Hirakawa Kenta Sumiyama Tomomi Shimogori Norihiro Okada A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8. PLoS ONE |
| title | A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8. |
| title_full | A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8. |
| title_fullStr | A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8. |
| title_full_unstemmed | A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8. |
| title_short | A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8. |
| title_sort | sine derived element constitutes a unique modular enhancer for mammalian diencephalic fgf8 |
| url | http://europepmc.org/articles/PMC3427154?pdf=render |
| work_keys_str_mv | AT akikonakanishi asinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT naokikobayashi asinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT asukasuzukihirano asinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT hidenorinishihara asinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT takeshisasaki asinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT mikahirakawa asinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT kentasumiyama asinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT tomomishimogori asinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT norihirookada asinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT akikonakanishi sinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT naokikobayashi sinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT asukasuzukihirano sinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT hidenorinishihara sinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT takeshisasaki sinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT mikahirakawa sinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT kentasumiyama sinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT tomomishimogori sinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 AT norihirookada sinederivedelementconstitutesauniquemodularenhancerformammaliandiencephalicfgf8 |