TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells

Publication date: 3 January 2017
Source:Cell Reports, Volume 18, Issue 1
Author(s): Per Ludvik Brattås, Marie E. Jönsson, Liana Fasching, Jenny Nelander Wahlestedt, Mansoureh Shahsavani, Ronny Falk, Anna Falk, Patric Jern, Malin Parmar, Johan Jakobsson
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.

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Teaser

Brattås et al. report that endogenous retroviruses are bound by TRIM28 in human neural progenitor cells. This results in the establishment of local heterochromatin that affects nearby gene expression, suggesting a role for endogenous retroviruses in the control of transcriptional networks in the developing human brain.


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