title: TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells.
abstract: Endogenous retroviruses (ERVs), which make up 8% of the human genome, have been proposed to participate in the control of gene regulatory networks. In this study, we find a region- and developmental stage-specific expression pattern of ERVs in the developing human brain, which is linked to a transcriptional network based on ERVs. We demonstrate that almost 10,000, primarily primate-specific, ERVs act as docking platforms for the co-repressor protein TRIM28 in human neural progenitor cells, which results in the establishment of local heterochromatin. Thereby, TRIM28 represses ERVs and consequently regulates the expression of neighboring genes. These results uncover a gene regulatory network based on ERVs that participates in control of gene expression of protein-coding transcripts important for brain development.
authors.affiliation: Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
authors.forename: Per Ludvik
authors.initials: PL
authors.lastname: Brattås
authors.affiliation: Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Jönsson
authors.affiliation: Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
authors.forename: Liana
authors.initials: L
authors.lastname: Fasching
authors.affiliation: Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Nelander Wahlestedt
authors.affiliation: Department of Neuroscience, Karolinska Institute, Retziusväg 8, 171 77 Stockholm, Sweden.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Shahsavani
authors.affiliation: Department of Neuroscience, Karolinska Institute, Retziusväg 8, 171 77 Stockholm, Sweden.
authors.forename: Ronny
authors.initials: R
authors.lastname: Falk
authors.affiliation: Department of Neuroscience, Karolinska Institute, Retziusväg 8, 171 77 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Falk
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Patric
authors.initials: P
authors.lastname: Jern
authors.affiliation: Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Parmar
authors.affiliation: Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden. Electronic address: johan.jakobsson@med.lu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Jakobsson
mesh_terms: D001921:Brain / Q000196:embryology / Q000821:virology; D020077:Endogenous Retroviruses / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D006801:Humans; D058953:Neural Stem Cells / Q000378:metabolism* / Q000821:virology*; D016366:Open Reading Frames / Q000235:genetics; D011485:Protein Binding; D015533:Transcriptional Activation / Q000235:genetics; D000076183:Tripartite Motif-Containing Protein 28 / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28
keywords: epigenetics; gene regulation; human development; neural stem cells; transposable elements