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Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9843970

PubChem

R-HSA-9843970

Description

The Human Silencing Hub (HUSH) complex comprises MPHOSPH8 (MPP8), Periphilin (PHPLN1), and TASOR, which appears to act as a scaffold that binds the other subunits (reviewed in Seczynska and Lehner 2023). The HUSH complex preferentially represses transcription of young LINE1 retroelements (Liu et al. 2018, Robbez-Masson et al. 2018) and some HIV integrants (Tchasovnikarova et al. 2015, Zhu et al. 2018, Chougui and Margottin-Goguet 2019).
The HUSH complex creates repressive chromatin in two ways (reviewed in Seczynska and Lehner 2023). Firstly, HUSH can cause spreading of existing heterochromatin by binding existing trimethylated H3K9 and recruiting SETDB1 to trimethylate H3K9 of adjacent nucleosomes (Tchasovnikarova et al. 2015). Secondly, HUSH can initiate heterochromatin by binding nascent transcripts via its PHPLN1 subunit and recruiting SETDB1 to trimethylate lysine-9 of histone H3 (H3K9) at the locus being transcribed (Seczynska et al. 2022).
By an uncharacterized mechanism, the HUSH complex targets long intronless cDNAs, such as those produced by retroelements, as well as unusually long exons of normal cellular genes (Seczynska et al. 2022). Introns somehow protect against silencing by HUSH, though actual splicing is not required (Seczynska et al. 2022). In mice, ZNF638 (NP220, Znf638 gene) recruits the HUSH complex to unintegrated murine leukemia virus (MLV) (Zhu et al. 2018) and in human cells ZNF638 (NP220) and HUSH silence recombinant adeno-associated viruses (Das et al. 2022). The potential recruitment of HUSH by ZNF638 to human retroelements is not yet demonstrated.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying entries **1 - 10** of 29 in total

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O60814	Histone H2B type 1-K	H2BC12 H2BFT HIRIP1 HIST1H2BK	view
P04908	Histone H2A type 1-B/E	H2AC4; H2AC8 H2AFA H2AFM HIST1H2AB HIST1H2AE	view
P06899	Histone H2B type 1-J	H2BC11 H2BFR HIST1H2BJ	view
P16104	Histone H2AX	H2AFX H2AX	view
P23527	Histone H2B type 1-O	H2BC17 H2BFH H2BFN HIST1H2BO	view
P33778	Histone H2B type 1-B	H2BC3 H2BFF HIST1H2BB	view
P57053	Histone H2B type F-S	H2BC12L H2BFS H2BS1	view
P58876	Histone H2B type 1-D	H2BC4; H2BC6; H2BC7; H2BC8; H2BC10 H2BC5 H2BFA H2BFB H2BFG H2BFH H2BFK H2BFL HIRIP2 HIST1H2BC HIST1H2BD HIST1H2BE HIST1H2BF HIST1H2BG HIST1H2BI	view
P62805	Histone H4	H4-16 H4/A H4/B H4/C H4/D H4/E H4/G H4/H H4/I H4/J H4/K H4/M H4/N H4/O H4C1; H4C2; H4C3; H4C4; H4C5; H4C6; H4C8; H4C9; H4C11; H4C12; H4C13; H4C14; H4C15; H4C16 H4F2 H4FA H4FB H4FC H4FD H4FE H4FG H4FH H4FI H4FJ H4FK H4FM H4FN H4FO HIST1H4A HIST1H4B HIST1H4C HIST1H4D HIST1H4E HIST1H4F HIST1H4H HIST1H4I HIST1H4J HIST1H4K HIST1H4L HIST2H4 HIST2H4A HIST2H4B HIST4H4	view
P62807	Histone H2B type 1-C/E/F/G/I	H2BC4; H2BC6; H2BC7; H2BC8; H2BC10 H2BC5 H2BFA H2BFB H2BFG H2BFH H2BFK H2BFL HIRIP2 HIST1H2BC HIST1H2BD HIST1H2BE HIST1H2BF HIST1H2BG HIST1H2BI	view

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