HMGXB4 Targets <i>Sleeping Beauty</i> Transposition to Germinal Stem Cells
Transposons are parasitic genetic elements that frequently hijack vital cellular processes of their host. HMGXB4 is a known Wnt signaling-regulating HMG-box protein, previously identified as a host-encoded factor of <i>Sleeping Beauty</i> (SB) transposition. Here, we show that HMGXB4 is...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7283 |
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| author | Anantharam Devaraj Manvendra Singh Suneel A Narayanavari Guo Yong Jiaxuan Chen Jichang Wang Mareike Becker Oliver Walisko Andrea Schorn Zoltán Cseresznyés Tamás Raskó Kathrin Radscheit Matthias Selbach Zoltán Ivics Zsuzsanna Izsvák |
| author_facet | Anantharam Devaraj Manvendra Singh Suneel A Narayanavari Guo Yong Jiaxuan Chen Jichang Wang Mareike Becker Oliver Walisko Andrea Schorn Zoltán Cseresznyés Tamás Raskó Kathrin Radscheit Matthias Selbach Zoltán Ivics Zsuzsanna Izsvák |
| author_sort | Anantharam Devaraj |
| collection | DOAJ |
| description | Transposons are parasitic genetic elements that frequently hijack vital cellular processes of their host. HMGXB4 is a known Wnt signaling-regulating HMG-box protein, previously identified as a host-encoded factor of <i>Sleeping Beauty</i> (SB) transposition. Here, we show that HMGXB4 is predominantly maternally expressed, and marks both germinal progenitor and somatic stem cells. SB piggybacks HMGXB4 to activate transposase expression and target transposition to germinal stem cells, thereby potentiating heritable transposon insertions. The <i>HMGXB4</i> promoter is located within an active chromatin domain, offering multiple looping possibilities with neighboring genomic regions. <i>HMGXB4</i> is activated by ERK2/MAPK1, ELK1 transcription factors, coordinating pluripotency and self-renewal pathways, but suppressed by the KRAB-ZNF/TRIM28 epigenetic repression machinery, also known to regulate transposable elements. At the post-translational level, SUMOylation regulates HMGXB4, which modulates binding affinity to its protein interaction partners and controls its transcriptional activator function via nucleolar compartmentalization. When expressed, HMGXB4 can participate in nuclear-remodeling protein complexes and transactivate target gene expression in vertebrates. Our study highlights HMGXB4 as an evolutionarily conserved host-encoded factor that assists <i>Tc1/Mariner</i> transposons to target the germline, which was necessary for their fixation and may explain their abundance in vertebrate genomes. |
| first_indexed | 2024-03-11T04:56:35Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:56:35Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e6cc226d10cf4f36a6067af588c94e7c2023-11-17T19:38:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248728310.3390/ijms24087283HMGXB4 Targets <i>Sleeping Beauty</i> Transposition to Germinal Stem CellsAnantharam Devaraj0Manvendra Singh1Suneel A Narayanavari2Guo Yong3Jiaxuan Chen4Jichang Wang5Mareike Becker6Oliver Walisko7Andrea Schorn8Zoltán Cseresznyés9Tamás Raskó10Kathrin Radscheit11Matthias Selbach12Zoltán Ivics13Zsuzsanna Izsvák14Max-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyDivision of Hematology, Gene and Cell Therapy, Paul-Ehrlich-Institute, Paul-Ehrlich-Strasse 51-59, 63225 Langen, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyDivision of Hematology, Gene and Cell Therapy, Paul-Ehrlich-Institute, Paul-Ehrlich-Strasse 51-59, 63225 Langen, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Society (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, GermanyTransposons are parasitic genetic elements that frequently hijack vital cellular processes of their host. HMGXB4 is a known Wnt signaling-regulating HMG-box protein, previously identified as a host-encoded factor of <i>Sleeping Beauty</i> (SB) transposition. Here, we show that HMGXB4 is predominantly maternally expressed, and marks both germinal progenitor and somatic stem cells. SB piggybacks HMGXB4 to activate transposase expression and target transposition to germinal stem cells, thereby potentiating heritable transposon insertions. The <i>HMGXB4</i> promoter is located within an active chromatin domain, offering multiple looping possibilities with neighboring genomic regions. <i>HMGXB4</i> is activated by ERK2/MAPK1, ELK1 transcription factors, coordinating pluripotency and self-renewal pathways, but suppressed by the KRAB-ZNF/TRIM28 epigenetic repression machinery, also known to regulate transposable elements. At the post-translational level, SUMOylation regulates HMGXB4, which modulates binding affinity to its protein interaction partners and controls its transcriptional activator function via nucleolar compartmentalization. When expressed, HMGXB4 can participate in nuclear-remodeling protein complexes and transactivate target gene expression in vertebrates. Our study highlights HMGXB4 as an evolutionarily conserved host-encoded factor that assists <i>Tc1/Mariner</i> transposons to target the germline, which was necessary for their fixation and may explain their abundance in vertebrate genomes.https://www.mdpi.com/1422-0067/24/8/7283<i>Sleeping Beauty</i>transposonHMGXB4transcriptional activatorH3K4me3NuRF |
| spellingShingle | Anantharam Devaraj Manvendra Singh Suneel A Narayanavari Guo Yong Jiaxuan Chen Jichang Wang Mareike Becker Oliver Walisko Andrea Schorn Zoltán Cseresznyés Tamás Raskó Kathrin Radscheit Matthias Selbach Zoltán Ivics Zsuzsanna Izsvák HMGXB4 Targets <i>Sleeping Beauty</i> Transposition to Germinal Stem Cells International Journal of Molecular Sciences <i>Sleeping Beauty</i> transposon HMGXB4 transcriptional activator H3K4me3 NuRF |
| title | HMGXB4 Targets <i>Sleeping Beauty</i> Transposition to Germinal Stem Cells |
| title_full | HMGXB4 Targets <i>Sleeping Beauty</i> Transposition to Germinal Stem Cells |
| title_fullStr | HMGXB4 Targets <i>Sleeping Beauty</i> Transposition to Germinal Stem Cells |
| title_full_unstemmed | HMGXB4 Targets <i>Sleeping Beauty</i> Transposition to Germinal Stem Cells |
| title_short | HMGXB4 Targets <i>Sleeping Beauty</i> Transposition to Germinal Stem Cells |
| title_sort | hmgxb4 targets i sleeping beauty i transposition to germinal stem cells |
| topic | <i>Sleeping Beauty</i> transposon HMGXB4 transcriptional activator H3K4me3 NuRF |
| url | https://www.mdpi.com/1422-0067/24/8/7283 |
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