Keep quiet: the HUSH complex in transcriptional silencing and disease

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 lysin...

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Published inNature structural & molecular biology Vol. 31; no. 1; pp. 11 - 22
Main Authors Müller, Iris, Helin, Kristian
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.01.2024
Nature Publishing Group
Subjects
631/208/176/2016
631/337/176/2016
Animals
Antiretroviral agents
Biochemistry
Biological Microscopy
Biomedical and Life Sciences
Cancer
Chromatin
Disease
Embryogenesis
Embryonic growth stage
Epigenetics
Gene regulation
Gene Silencing
Genomes
Histones
Histones - genetics
Histones - metabolism
Humans
Life Sciences
Lysine
Mammals - genetics
Membrane Biology
Methylation
Mice
Molecular modelling
Neoplasms - genetics
Nuclear Proteins - metabolism
Protein Structure
Retroelements
Review Article
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Summary: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. Here, the authors discuss the various roles of the HUSH transcriptional silencing complex and its dysregulation in disease.
Bibliography:ObjectType-Article-2
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ISSN:1545-9993
1545-9985
DOI:10.1038/s41594-023-01173-7