Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers
© 2016 Elsevier Inc. Generic spinal motor neuron identity is established by cooperative binding of programming transcription factors (TFs), Isl1 and Lhx3, to motor-neuron-specific enhancers. How expression of effector genes is maintained following downregulation of programming TFs in maturing neuron...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/135733 |
| _version_ | 1826195387101216768 |
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| author | Rhee, Ho Sung Closser, Michael Guo, Yuchun Bashkirova, Elizaveta V Tan, G Christopher Gifford, David K Wichterle, Hynek |
| author_facet | Rhee, Ho Sung Closser, Michael Guo, Yuchun Bashkirova, Elizaveta V Tan, G Christopher Gifford, David K Wichterle, Hynek |
| author_sort | Rhee, Ho Sung |
| collection | MIT |
| description | © 2016 Elsevier Inc. Generic spinal motor neuron identity is established by cooperative binding of programming transcription factors (TFs), Isl1 and Lhx3, to motor-neuron-specific enhancers. How expression of effector genes is maintained following downregulation of programming TFs in maturing neurons remains unknown. High-resolution exonuclease (ChIP-exo) mapping revealed that the majority of enhancers established by programming TFs are rapidly deactivated following Lhx3 downregulation in stem-cell-derived hypaxial motor neurons. Isl1 is released from nascent motor neuron enhancers and recruited to new enhancers bound by clusters of Onecut1 in maturing neurons. Synthetic enhancer reporter assays revealed that Isl1 operates as an integrator factor, translating the density of Lhx3 or Onecut1 binding sites into transient enhancer activity. Importantly, independent Isl1/Lhx3- and Isl1/Onecut1-bound enhancers contribute to sustained expression of motor neuron effector genes, demonstrating that outwardly stable expression of terminal effector genes in postmitotic neurons is controlled by a dynamic relay of stage-specific enhancers. |
| first_indexed | 2024-09-23T10:11:52Z |
| format | Article |
| id | mit-1721.1/135733 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:11:52Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1357332022-04-01T16:18:08Z Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers Rhee, Ho Sung Closser, Michael Guo, Yuchun Bashkirova, Elizaveta V Tan, G Christopher Gifford, David K Wichterle, Hynek © 2016 Elsevier Inc. Generic spinal motor neuron identity is established by cooperative binding of programming transcription factors (TFs), Isl1 and Lhx3, to motor-neuron-specific enhancers. How expression of effector genes is maintained following downregulation of programming TFs in maturing neurons remains unknown. High-resolution exonuclease (ChIP-exo) mapping revealed that the majority of enhancers established by programming TFs are rapidly deactivated following Lhx3 downregulation in stem-cell-derived hypaxial motor neurons. Isl1 is released from nascent motor neuron enhancers and recruited to new enhancers bound by clusters of Onecut1 in maturing neurons. Synthetic enhancer reporter assays revealed that Isl1 operates as an integrator factor, translating the density of Lhx3 or Onecut1 binding sites into transient enhancer activity. Importantly, independent Isl1/Lhx3- and Isl1/Onecut1-bound enhancers contribute to sustained expression of motor neuron effector genes, demonstrating that outwardly stable expression of terminal effector genes in postmitotic neurons is controlled by a dynamic relay of stage-specific enhancers. 2021-10-27T20:29:02Z 2021-10-27T20:29:02Z 2016 2019-05-29T14:13:22Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135733 Rhee, H. S., et al. "Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers." Neuron 92 6 (2016): 1252-65. en 10.1016/J.NEURON.2016.11.037 Neuron Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Rhee, Ho Sung Closser, Michael Guo, Yuchun Bashkirova, Elizaveta V Tan, G Christopher Gifford, David K Wichterle, Hynek Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers |
| title | Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers |
| title_full | Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers |
| title_fullStr | Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers |
| title_full_unstemmed | Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers |
| title_short | Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers |
| title_sort | expression of terminal effector genes in mammalian neurons is maintained by a dynamic relay of transient enhancers |
| url | https://hdl.handle.net/1721.1/135733 |
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