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HMGXB4 targets Sleeping Beauty transposition to germinal stem cells

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Item Type:Article
Title:HMGXB4 targets Sleeping Beauty transposition to germinal stem cells
Creators Name:Devaraj, A. and Singh, M. and Narayanavari, S.A. and Yong, G. and Chen, J. and Wang, J. and Becker, M. and Walisko, O. and Schorn, A. and Cseresznyés, Z. and Raskó, T. and Radscheit, K. and Selbach, M. and Ivics, Z. and Izsvak, Z.
Abstract: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 Sleeping Beauty (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 HMGXB4 promoter is located within an active chromatin domain, offering multiple looping possibilities with neighboring genomic regions. HMGXB4 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 Tc1/Mariner transposons to target the germline, which was necessary for their fixation and may explain their abundance in vertebrate genomes.
Keywords:Sleeping Beauty, Transposon, HMGXB4, Transcriptional Activator, H3K4me3, NuRF, MLL Complex, Chromatin Remodeling, Nucleolus, BAP18/C17orf49, SUMOylation, Germline, Germinal Stem Cell, Wnt Signaling, Chromatin Domain Boundary, Animals
Source:International Journal of Molecular Sciences
Page Range:7283
Date:14 April 2023
Official Publication:https://doi.org/10.3390/ijms24087283
PubMed:View item in PubMed

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