Keep quiet: The HUSH complex in transcriptional silencing and disease Review
| Authors: | Müller, I.; Helin, K. |
| Review Title: | Keep quiet: The HUSH complex in transcriptional silencing and disease |
| Abstract: | The human silencing hub (HUSH) complex is an epigenetic repressor complex whose role has emerged as an important guardian of genome integrity. It protects the genome from exogenous DNA invasion and regulates endogenous retroelements by recruiting histone methyltransferases catalyzing histone 3 lysine 9 trimethylation (H3K9me3) and additional proteins involved in chromatin compaction. In particular, its regulation of transcriptionally active LINE1 retroelements, by binding to and neutralizing LINE1 transcripts, has been well characterized. HUSH is required for mouse embryogenesis and is associated with disease, in particular cancer. Here we provide insights into the structural and biochemical features of the HUSH complex. Furthermore, we discuss the molecular mechanisms by which the HUSH complex is recruited to specific genomic regions and how it silences transcription. Finally, we discuss the role of HUSH complex members in mammalian development, antiretroviral immunity, and diseases such as cancer. © 2024, Springer Nature America, Inc. |
| Keywords: | review; nonhuman; mouse; gene expression; embryo development; histone methyltransferase; chromatin; histone h3; lysine; etiology; retroposon; human; long interspersed nuclear element 1 |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 31 |
| Issue: | 1 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-01-01 |
| Start Page: | 11 |
| End Page: | 22 |
| Language: | English |
| DOI: | 10.1038/s41594-023-01173-7 |
| PUBMED: | 38216658 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus |
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