Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity
The mammalian imprinted Dlk1-Dio3 locus produces multiple long non-coding RNAs (lncRNAs) from the maternally inherited allele, including Meg3 (i.e., Gtl2) in the mammalian genome. Although this locus has well-characterized functions in stem cell and tumor contexts, its role during neural development...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2018-10-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/38080 |
| _version_ | 1828376335302524928 |
|---|---|
| author | Ya-Ping Yen Wen-Fu Hsieh Ya-Yin Tsai Ya-Lin Lu Ee Shan Liau Ho-Chiang Hsu Yen-Chung Chen Ting-Chun Liu Mien Chang Joye Li Shau-Ping Lin Jui-Hung Hung Jun-An Chen |
| author_facet | Ya-Ping Yen Wen-Fu Hsieh Ya-Yin Tsai Ya-Lin Lu Ee Shan Liau Ho-Chiang Hsu Yen-Chung Chen Ting-Chun Liu Mien Chang Joye Li Shau-Ping Lin Jui-Hung Hung Jun-An Chen |
| author_sort | Ya-Ping Yen |
| collection | DOAJ |
| description | The mammalian imprinted Dlk1-Dio3 locus produces multiple long non-coding RNAs (lncRNAs) from the maternally inherited allele, including Meg3 (i.e., Gtl2) in the mammalian genome. Although this locus has well-characterized functions in stem cell and tumor contexts, its role during neural development is unknown. By profiling cell types at each stage of embryonic stem cell-derived motor neurons (ESC~MNs) that recapitulate spinal cord development, we uncovered that lncRNAs expressed from the Dlk1-Dio3 locus are predominantly and gradually enriched in rostral motor neurons (MNs). Mechanistically, Meg3 and other Dlk1-Dio3 locus-derived lncRNAs facilitate Ezh2/Jarid2 interactions. Loss of these lncRNAs compromises the H3K27me3 landscape, leading to aberrant expression of progenitor and caudal Hox genes in postmitotic MNs. Our data thus illustrate that these lncRNAs in the Dlk1-Dio3 locus, particularly Meg3, play a critical role in maintaining postmitotic MN cell fate by repressing progenitor genes and they shape MN subtype identity by regulating Hox genes. |
| first_indexed | 2024-04-14T07:58:37Z |
| format | Article |
| id | doaj.art-916274e7147f4697b3534223d5f514e8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:58:37Z |
| publishDate | 2018-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-916274e7147f4697b3534223d5f514e82022-12-22T02:04:57ZengeLife Sciences Publications LtdeLife2050-084X2018-10-01710.7554/eLife.38080Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identityYa-Ping Yen0https://orcid.org/0000-0003-2264-8126Wen-Fu Hsieh1Ya-Yin Tsai2https://orcid.org/0000-0002-9152-7646Ya-Lin Lu3Ee Shan Liau4https://orcid.org/0000-0002-4115-5573Ho-Chiang Hsu5Yen-Chung Chen6https://orcid.org/0000-0002-8529-1251Ting-Chun Liu7Mien Chang8Joye Li9Shau-Ping Lin10Jui-Hung Hung11https://orcid.org/0000-0003-2208-9213Jun-An Chen12https://orcid.org/0000-0001-9870-3203Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China; Institute of Biotechnology, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan, Republic of ChinaInstitute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan, Republic of ChinaInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of ChinaInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of ChinaInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of ChinaInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of ChinaInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of ChinaInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of ChinaInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of ChinaInstitute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan, Republic of ChinaInstitute of Biotechnology, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan, Republic of ChinaInstitute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan, Republic of China; Department of Computer Science, National Chiao Tung University, Hsinchu, Taiwan, Republic of ChinaInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of ChinaThe mammalian imprinted Dlk1-Dio3 locus produces multiple long non-coding RNAs (lncRNAs) from the maternally inherited allele, including Meg3 (i.e., Gtl2) in the mammalian genome. Although this locus has well-characterized functions in stem cell and tumor contexts, its role during neural development is unknown. By profiling cell types at each stage of embryonic stem cell-derived motor neurons (ESC~MNs) that recapitulate spinal cord development, we uncovered that lncRNAs expressed from the Dlk1-Dio3 locus are predominantly and gradually enriched in rostral motor neurons (MNs). Mechanistically, Meg3 and other Dlk1-Dio3 locus-derived lncRNAs facilitate Ezh2/Jarid2 interactions. Loss of these lncRNAs compromises the H3K27me3 landscape, leading to aberrant expression of progenitor and caudal Hox genes in postmitotic MNs. Our data thus illustrate that these lncRNAs in the Dlk1-Dio3 locus, particularly Meg3, play a critical role in maintaining postmitotic MN cell fate by repressing progenitor genes and they shape MN subtype identity by regulating Hox genes.https://elifesciences.org/articles/38080motor neuronlong noncoding RNA (lncRNA)HoxEzh2H3K27me3Meg3 |
| spellingShingle | Ya-Ping Yen Wen-Fu Hsieh Ya-Yin Tsai Ya-Lin Lu Ee Shan Liau Ho-Chiang Hsu Yen-Chung Chen Ting-Chun Liu Mien Chang Joye Li Shau-Ping Lin Jui-Hung Hung Jun-An Chen Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity eLife motor neuron long noncoding RNA (lncRNA) Hox Ezh2 H3K27me3 Meg3 |
| title | Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity |
| title_full | Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity |
| title_fullStr | Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity |
| title_full_unstemmed | Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity |
| title_short | Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity |
| title_sort | dlk1 dio3 locus derived lncrnas perpetuate postmitotic motor neuron cell fate and subtype identity |
| topic | motor neuron long noncoding RNA (lncRNA) Hox Ezh2 H3K27me3 Meg3 |
| url | https://elifesciences.org/articles/38080 |
| work_keys_str_mv | AT yapingyen dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT wenfuhsieh dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT yayintsai dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT yalinlu dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT eeshanliau dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT hochianghsu dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT yenchungchen dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT tingchunliu dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT mienchang dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT joyeli dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT shaupinglin dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT juihunghung dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity AT junanchen dlk1dio3locusderivedlncrnasperpetuatepostmitoticmotorneuroncellfateandsubtypeidentity |