Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor
Abstract Transcriptional repression of Nanog is an important hallmark of stem cell differentiation. Chromatin modifications have been linked to the epigenetic profile of the Nanog gene, but whether chromatin organization actually plays a causal role in Nanog regulation is still unclear. Here, we rep...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Epigenetics & Chromatin |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13072-020-00336-w |
| _version_ | 1828764553271312384 |
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| author | Francisco J. González-Rico Cristina Vicente-García Almudena Fernández Diego Muñoz-Santos Lluís Montoliu Antonio Morales-Hernández Jaime M. Merino Angel-Carlos Román Pedro M. Fernández-Salguero |
| author_facet | Francisco J. González-Rico Cristina Vicente-García Almudena Fernández Diego Muñoz-Santos Lluís Montoliu Antonio Morales-Hernández Jaime M. Merino Angel-Carlos Román Pedro M. Fernández-Salguero |
| author_sort | Francisco J. González-Rico |
| collection | DOAJ |
| description | Abstract Transcriptional repression of Nanog is an important hallmark of stem cell differentiation. Chromatin modifications have been linked to the epigenetic profile of the Nanog gene, but whether chromatin organization actually plays a causal role in Nanog regulation is still unclear. Here, we report that the formation of a chromatin loop in the Nanog locus is concomitant to its transcriptional downregulation during human NTERA-2 cell differentiation. We found that two Alu elements flanking the Nanog gene were bound by the aryl hydrocarbon receptor (AhR) and the insulator protein CTCF during cell differentiation. Such binding altered the profile of repressive histone modifications near Nanog likely leading to gene insulation through the formation of a chromatin loop between the two Alu elements. Using a dCAS9-guided proteomic screening, we found that interaction of the histone methyltransferase PRMT1 and the chromatin assembly factor CHAF1B with the Alu elements flanking Nanog was required for chromatin loop formation and Nanog repression. Therefore, our results uncover a chromatin-driven, retrotransposon-regulated mechanism for the control of Nanog expression during cell differentiation. |
| first_indexed | 2024-12-11T02:25:21Z |
| format | Article |
| id | doaj.art-434edba6cc424458a09bce6320a68889 |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-12-11T02:25:21Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-434edba6cc424458a09bce6320a688892022-12-22T01:23:57ZengBMCEpigenetics & Chromatin1756-89352020-03-0113111310.1186/s13072-020-00336-wAlu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptorFrancisco J. González-Rico0Cristina Vicente-García1Almudena Fernández2Diego Muñoz-Santos3Lluís Montoliu4Antonio Morales-Hernández5Jaime M. Merino6Angel-Carlos Román7Pedro M. Fernández-Salguero8Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de ExtremaduraDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC)Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de ExtremaduraDepartamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de ExtremaduraDepartamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de ExtremaduraDepartamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de ExtremaduraAbstract Transcriptional repression of Nanog is an important hallmark of stem cell differentiation. Chromatin modifications have been linked to the epigenetic profile of the Nanog gene, but whether chromatin organization actually plays a causal role in Nanog regulation is still unclear. Here, we report that the formation of a chromatin loop in the Nanog locus is concomitant to its transcriptional downregulation during human NTERA-2 cell differentiation. We found that two Alu elements flanking the Nanog gene were bound by the aryl hydrocarbon receptor (AhR) and the insulator protein CTCF during cell differentiation. Such binding altered the profile of repressive histone modifications near Nanog likely leading to gene insulation through the formation of a chromatin loop between the two Alu elements. Using a dCAS9-guided proteomic screening, we found that interaction of the histone methyltransferase PRMT1 and the chromatin assembly factor CHAF1B with the Alu elements flanking Nanog was required for chromatin loop formation and Nanog repression. Therefore, our results uncover a chromatin-driven, retrotransposon-regulated mechanism for the control of Nanog expression during cell differentiation.http://link.springer.com/article/10.1186/s13072-020-00336-wAlu retrotransposonsAryl hydrocarbon receptorDifferentiationNanogChromatin conformation |
| spellingShingle | Francisco J. González-Rico Cristina Vicente-García Almudena Fernández Diego Muñoz-Santos Lluís Montoliu Antonio Morales-Hernández Jaime M. Merino Angel-Carlos Román Pedro M. Fernández-Salguero Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor Epigenetics & Chromatin Alu retrotransposons Aryl hydrocarbon receptor Differentiation Nanog Chromatin conformation |
| title | Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor |
| title_full | Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor |
| title_fullStr | Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor |
| title_full_unstemmed | Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor |
| title_short | Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor |
| title_sort | alu retrotransposons modulate nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor |
| topic | Alu retrotransposons Aryl hydrocarbon receptor Differentiation Nanog Chromatin conformation |
| url | http://link.springer.com/article/10.1186/s13072-020-00336-w |
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