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Regulation of endogenous retroelements by KRAB-ZFP proteins

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9843940

PubChem

R-HSA-9843940

Description

Krüppel-associated box domain (KRAB) zinc finger proteins (KRAB-ZFPs) contain a transcriptionally repressive N-terminal domain, the KRAB domain, and a C-terminal domain, the ZFP domain, that contains 2-40 zinc fingers and binds specific sequences of DNA (reviewed in Ecco et al. 2017, Yang et al. 2017). The human genome contains about 352 (Lukic et al. 2014), 378 (de Tribolet-Hardy et al. 2023), or 423 (Huntley et al. 2006) KRAB-ZFP genes, making them the largest family of transcription regulators.
About two thirds or more of KRAB-ZFPs bind transposable elements (Schmitges et al. 2016, Imbeault et al. 2017, de Tribolet-Hardy et al. 2023) and KRAB-ZFPs appear to coevolve with retroelements such that a KRAB-ZFP binds and transcriptionally silences a specific set of retroelements (reviewed in Ecco et al. 2017). The number of KRAB-ZFP genes correlates with the number of retroelements in mammalian genomes and younger retroelements bind fewer KRAB-ZFPs, suggesting an "arms race" in which the evolution of new KRAB-ZFPs is driven by and lags the appearance of new transposable elements (Thomas and Schneider 2011, Jacobs et al. 2014, Imbeault et al. 2017, reviewed in Ecco et al. 2017, Yang et al. 2017).
The repressive action of KRAB-ZFPs is mediated by the scaffold protein TRIM28 (also called KAP1), the RBCC domain of which binds the N-terminal KRAB domains of KRAB-ZFPs (Friedman et al. 1996). TRIM28 autoSUMOylates and recruits effectors, such as the histone H3 lysine-9 trimethyltransferase SETDB1 (also called ESET) (Schultz et al. 2002) and the NuRD repressor complex (Schultz et al. 2001).
The HUSH complex (MPHOSPH8:TASOR:PPHLN1) plays a nonredundant role with TRIM28 in silencing some young LINE1 retroelements, which are only weakly repressed by TRIM28 or HUSH alone (Robbez-Masson et al. 2018).

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SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying entries **1 - 10** of 38 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
O95983	Methyl-CpG-binding domain protein 3	MBD3	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
P17039	Zinc finger protein 30	KOX28 ZNF30	view
P23527	Histone H2B type 1-O	H2BC17 H2BFH H2BFN HIST1H2BO	view
P33778	Histone H2B type 1-B	H2BC3 H2BFF HIST1H2BB	view
P35789	Zinc finger protein 93	ZNF505 ZNF93	view
P45973	Chromobox protein homolog 5	CBX5 HP1A	view

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