In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation
Recent evidence has determined that the conserved X chromosome mega-structures controlled by the Firre and Dxz4 loci are not required for X chromosome inactivation (XCI) in cell lines. Here, we examined the in vivo contribution of these loci by generating mice carrying a single or double deletion of...
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| Format: | Article |
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eLife Sciences Publications Ltd
2019-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/47214 |
| _version_ | 1811252991069519872 |
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| author | Daniel Andergassen Zachary D Smith Jordan P Lewandowski Chiara Gerhardinger Alexander Meissner John L Rinn |
| author_facet | Daniel Andergassen Zachary D Smith Jordan P Lewandowski Chiara Gerhardinger Alexander Meissner John L Rinn |
| author_sort | Daniel Andergassen |
| collection | DOAJ |
| description | Recent evidence has determined that the conserved X chromosome mega-structures controlled by the Firre and Dxz4 loci are not required for X chromosome inactivation (XCI) in cell lines. Here, we examined the in vivo contribution of these loci by generating mice carrying a single or double deletion of Firre and Dxz4. We found that these mutants are viable, fertile and show no defect in random or imprinted XCI. However, the lack of these elements results in many dysregulated genes on autosomes in an organ-specific manner. By comparing the dysregulated genes between the single and double deletion, we identified superloop, megadomain, and Firre locus-dependent gene sets. The largest transcriptional effect was observed in all strains lacking the Firre locus, indicating that this locus is the main driver for these autosomal expression signatures. Collectively, these findings suggest that these X-linked loci are involved in autosomal gene regulation rather than XCI biology. |
| first_indexed | 2024-04-12T16:43:01Z |
| format | Article |
| id | doaj.art-1c2cab850748461eaf421c1d07f7c435 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:43:01Z |
| publishDate | 2019-11-01 |
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| spelling | doaj.art-1c2cab850748461eaf421c1d07f7c4352022-12-22T03:24:41ZengeLife Sciences Publications LtdeLife2050-084X2019-11-01810.7554/eLife.47214In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulationDaniel Andergassen0https://orcid.org/0000-0003-1196-4289Zachary D Smith1Jordan P Lewandowski2Chiara Gerhardinger3Alexander Meissner4https://orcid.org/0000-0001-8646-7469John L Rinn5https://orcid.org/0000-0002-7231-7539Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United StatesDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, GermanyDepartment of Biochemistry, University of Colorado Boulder, Boulder, United StatesRecent evidence has determined that the conserved X chromosome mega-structures controlled by the Firre and Dxz4 loci are not required for X chromosome inactivation (XCI) in cell lines. Here, we examined the in vivo contribution of these loci by generating mice carrying a single or double deletion of Firre and Dxz4. We found that these mutants are viable, fertile and show no defect in random or imprinted XCI. However, the lack of these elements results in many dysregulated genes on autosomes in an organ-specific manner. By comparing the dysregulated genes between the single and double deletion, we identified superloop, megadomain, and Firre locus-dependent gene sets. The largest transcriptional effect was observed in all strains lacking the Firre locus, indicating that this locus is the main driver for these autosomal expression signatures. Collectively, these findings suggest that these X-linked loci are involved in autosomal gene regulation rather than XCI biology.https://elifesciences.org/articles/47214X chromosome inactivationFIRREDXZ4chromosome structureNHCCIntra-chromosomal organization |
| spellingShingle | Daniel Andergassen Zachary D Smith Jordan P Lewandowski Chiara Gerhardinger Alexander Meissner John L Rinn In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation eLife X chromosome inactivation FIRRE DXZ4 chromosome structure NHCC Intra-chromosomal organization |
| title | In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation |
| title_full | In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation |
| title_fullStr | In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation |
| title_full_unstemmed | In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation |
| title_short | In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation |
| title_sort | in vivo firre and dxz4 deletion elucidates roles for autosomal gene regulation |
| topic | X chromosome inactivation FIRRE DXZ4 chromosome structure NHCC Intra-chromosomal organization |
| url | https://elifesciences.org/articles/47214 |
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