A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation
HOTAIRM1 is unlike most long non-coding RNAs in that its sequence is highly conserved across mammals. Such evolutionary conservation points to it having a role in key cellular processes. We previously reported that HOTAIRM1 is required to curb premature activation of downstream HOXA genes in a cell...
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| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | RNA Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15476286.2023.2258028 |
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| author | Dana Segal Samy Coulombe Jasper Sim Josée Dostie |
| author_facet | Dana Segal Samy Coulombe Jasper Sim Josée Dostie |
| author_sort | Dana Segal |
| collection | DOAJ |
| description | HOTAIRM1 is unlike most long non-coding RNAs in that its sequence is highly conserved across mammals. Such evolutionary conservation points to it having a role in key cellular processes. We previously reported that HOTAIRM1 is required to curb premature activation of downstream HOXA genes in a cell model recapitulating their sequential induction during development. We found that it regulates 3’ HOXA gene expression by a mechanism involving epigenetic and three-dimensional chromatin changes. Here we show that HOTAIRM1 participates in proper progression through the early stages of neuronal differentiation. We found that it can associate with the HOXA1 transcription factor and contributes to its downstream transcriptional program. Particularly, HOTAIRM1 affects the NANOG/POU5F1/SOX2 core pluripotency network maintaining an undifferentiated cell state. HOXA1 depletion similarly perturbed expression of these pluripotent factors, suggesting that HOTAIRM1 is a modulator of this transcription factor pathway. Also, given that binding of HOTAIRM1 to HOXA1 was observed in different cell types and species, our results point to this ribonucleoprotein complex as an integral part of a conserved HOTAIRM1-HOXA1 regulatory axis modulating the transition from a pluripotent to a differentiated neuronal state. |
| format | Article |
| id | doaj-art-b3613b91bd594c8ea80fc9da25d1f3ec |
| institution | OA Journals |
| issn | 1547-6286 1555-8584 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | RNA Biology |
| spelling | doaj-art-b3613b91bd594c8ea80fc9da25d1f3ec2025-08-20T02:17:01ZengTaylor & Francis GroupRNA Biology1547-62861555-85842023-12-012011523153910.1080/15476286.2023.2258028A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiationDana Segal0Samy Coulombe1Jasper Sim2Josée Dostie3Department of Biochemistry, and Rosalind & Morris Goodman Cancer Institute, McGill University, Montréal, Québec, CanadaDepartment of Biochemistry, and Rosalind & Morris Goodman Cancer Institute, McGill University, Montréal, Québec, CanadaDepartment of Biochemistry, and Rosalind & Morris Goodman Cancer Institute, McGill University, Montréal, Québec, CanadaDepartment of Biochemistry, and Rosalind & Morris Goodman Cancer Institute, McGill University, Montréal, Québec, CanadaHOTAIRM1 is unlike most long non-coding RNAs in that its sequence is highly conserved across mammals. Such evolutionary conservation points to it having a role in key cellular processes. We previously reported that HOTAIRM1 is required to curb premature activation of downstream HOXA genes in a cell model recapitulating their sequential induction during development. We found that it regulates 3’ HOXA gene expression by a mechanism involving epigenetic and three-dimensional chromatin changes. Here we show that HOTAIRM1 participates in proper progression through the early stages of neuronal differentiation. We found that it can associate with the HOXA1 transcription factor and contributes to its downstream transcriptional program. Particularly, HOTAIRM1 affects the NANOG/POU5F1/SOX2 core pluripotency network maintaining an undifferentiated cell state. HOXA1 depletion similarly perturbed expression of these pluripotent factors, suggesting that HOTAIRM1 is a modulator of this transcription factor pathway. Also, given that binding of HOTAIRM1 to HOXA1 was observed in different cell types and species, our results point to this ribonucleoprotein complex as an integral part of a conserved HOTAIRM1-HOXA1 regulatory axis modulating the transition from a pluripotent to a differentiated neuronal state.https://www.tandfonline.com/doi/10.1080/15476286.2023.2258028LncRNAHOXA1HOTAIRM1epigeneticschromatinpluripotency |
| spellingShingle | Dana Segal Samy Coulombe Jasper Sim Josée Dostie A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation RNA Biology LncRNA HOXA1 HOTAIRM1 epigenetics chromatin pluripotency |
| title | A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation |
| title_full | A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation |
| title_fullStr | A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation |
| title_full_unstemmed | A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation |
| title_short | A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation |
| title_sort | conserved hotairm1 hoxa1 regulatory axis contributes early to neuronal differentiation |
| topic | LncRNA HOXA1 HOTAIRM1 epigenetics chromatin pluripotency |
| url | https://www.tandfonline.com/doi/10.1080/15476286.2023.2258028 |
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