TRIM28 controls a primate-specific gene regulatory network based on endogenous retroviruses in human neural progenitor cells
Event details
| Date | 25.11.2016 |
| Hour | 08:15 |
| Speaker |
Johan Jakobsson PhD Associate Professor of Neuroscience Laboratory of Molecular Neurogenetics Wallenberg Neuroscience Center Lund Stem Cell Center Lund University Sweden |
| Location | |
| Category | Conferences - Seminars |
The complexity of human brain development differs markedly from other mammals and is thought be important for the emergence of higher cognitive functions. However, the precise genetic changes, as well as the existence of human-specific gene regulatory networks underlying the evolution of the human brain remains poorly explored. Most of our knowledge about human brain development is restricted to evolutionary conserved developmental pathways, while much less is known about primate- and human-specific developmental mechanisms. Identification of novel mechanisms that regulate human brain development is important for our understanding of the human brain and may also provide new links to the biology of human brain disorders.
About 8% of the human genome is composed of endogenous retroviruses (ERVs). These sequences are derived from retroviruses that have invaded vertebrate hosts for millions of years leaving traces as inherited ERVs through germ line infection and subsequent transposition. Several studies have found that ERV transcription is tightly controlled at multiple levels in early human development and they 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 several thousand ERVs, many that are primate-specific, act as docking platforms for the epigenetic co-repressor protein TRIM28, which results in the establishment of local heterochromatin around these ERVs. This repressive transcriptional network modulates expression of protein-coding transcripts important for brain development, thereby providing an additional layer of transcriptional regulation. Our findings open up for several exciting future studies on the role of ERVs as potential drivers of human brain evolution, their contribution to individual variation and the implication in human brain disorders.
About 8% of the human genome is composed of endogenous retroviruses (ERVs). These sequences are derived from retroviruses that have invaded vertebrate hosts for millions of years leaving traces as inherited ERVs through germ line infection and subsequent transposition. Several studies have found that ERV transcription is tightly controlled at multiple levels in early human development and they 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 several thousand ERVs, many that are primate-specific, act as docking platforms for the epigenetic co-repressor protein TRIM28, which results in the establishment of local heterochromatin around these ERVs. This repressive transcriptional network modulates expression of protein-coding transcripts important for brain development, thereby providing an additional layer of transcriptional regulation. Our findings open up for several exciting future studies on the role of ERVs as potential drivers of human brain evolution, their contribution to individual variation and the implication in human brain disorders.
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- Prof Didier Trono
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- Séverine Reynard