Abstract
Endogenous retroviruses (ERVs) are repetitive sequences in the genome, belonging to the retrotransposon family. During the course of life, ERVs are associated with multiple aspects of chromatin and transcriptional regulation in development and pathological conditions. In mammalian embryos, ERVs are extensively activated in early embryo development, but with a highly restricted spatial-temporal pattern; and they are drastically silenced during differentiation with exceptions in extraembryonic tissue and germlines. The dynamic activation pattern of ERVs raises questions about how ERVs are regulated in the life cycle and whether they are functionally important to cell fate decision during early embryo and somatic cell development. Therefore, in this review, we focus on the pieces of evidence demonstrating regulations and functions of ERVs during stem cell differentiation, which suggests that ERV activation is not a passive result of cell fate transition but the active epigenetic and transcriptional regulation during mammalian development and stem cell differentiation.
Highlights
Endogenous retroviruses (ERVs) belong to a Class family of retrotransposon elements in the genome
Together with DNA transposons, they are known as transposable elements (TEs), which are derived from DNA fragments able to transpose within the genome
Human DUX4 is kept silenced in differentiated tissues, as aberrant activation of DUX4 in muscle tissue upregulates HERVL, leading to unscheduled transcription activation of early embryonic genes which eventually resulted in facioscapulohumeral muscular dystrophy [10]
Summary
ERVs belong to a Class family of retrotransposon elements in the genome. Together with DNA transposons, they are known as transposable elements (TEs), which are derived from DNA fragments able to transpose within the genome. ERVs and other family members of TEs used to be considered as “junk DNA,” but with the technological advancement in genome-wide expression and epigenetic profiling, we started to appreciate more on their functional contribution to development and diseases. The LTR regions of ERVs possess binding sites for a broad scope of transcription factors to interact with the host gene regulatory machinery and achieve precise control of ERV activity [7]. ERVs can affect genome-wide transcription through multiple layers of regulation as discussed below Their activities should be tightly controlled in the mammalian genome to coordinate with proper development and cell fate decision process. We will discuss in detail about the current knowledge on the functions of ERV in chromatin and transcription regulation, how these functions are achieved, and how they contribute to cell fate decision during mammalian embryonic development and stem cell differentiation
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