HMGXB4 Targets Sleeping Beauty Transposition to Germinal Stem Cells

Devaraj, Anantharam, Singh, Manvendra, Narayanavari, Suneel A, Yong, Guo, Chen, Jiaxuan, Wang, Jichang, Becker, Mareike, Walisko, Oliver, Schorn, Andrea, Cseresznyés, Zoltán, Raskó, Tamás, Radscheit, Kathrin, Selbach, Matthias, Ivics, Zoltán, Izsvák, Zsuzsanna (April 2023) HMGXB4 Targets Sleeping Beauty Transposition to Germinal Stem Cells. International Journal of Molecular Sciences, 24 (8). p. 7283. ISSN 1661-6596

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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.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transposons
CSHL Authors:	Schorn, Andrea
Communities:	CSHL labs > Schorn lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	14 April 2023
Date Deposited:	28 Sep 2023 17:47
Last Modified:	08 Jan 2024 19:08
PMCID:	PMC10138897
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41033

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