Reactome | SETDB1 in ATF7IP:SETDB1:SUMO2-6K-TRIM28:KRAB-ZFP:retroelement trimethylates lysine-9 of histone H3 in nucleosomes

SETDB1 in ATF7IP:SETDB1:SUMO2-6K-TRIM28:KRAB-ZFP:retroelement trimethylates lysine-9 of histone H3 in nucleosomes

Stable Identifier

R-HSA-9842833

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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SETDB1 in ATF7IP:SETDB1:SUMO2-6K-TRIM28:KRAB-ZFP:retroelement trimethylates lysine-9 of histone H3 in nucleosomes

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SETDB1 bound to TRIM28 trimethylates lysine-9 of histone H3 (H3K9) (Schultz et al. 2002, Wang et al. 2003, Basavapathruni et al. 2016). ATF7IP (hAM, mAM) binds SETDB1 in the nucleus and enhances the methyltransferase activity of SETDB1 (Wang et al. 2003, Basavapathruni et al. 2016, also inferred from mouse homologs in Tsusaka et al. 2019, 2020). In mouse embryos, knockout of Trim28 causes a reduction in H3K9 trimethylation and increased expression of transposable elements such as intracisternal A-type particels (IAPs) (Rowe et al. 2010). In mouse embryonic stem cells, SETDB1 (Matsui et al. 2010) and the SETDB1-interacting region of ATF7IP Tsusaka et al. 2020) are required for silencing of retrotransposons. In mouse embryonic stem cells, endogenous retroviruses are targeted by KRAB‑ZFPs, TRIM28, and SETDB1 and become DNA methylated, likely due to interaction between TRIM28 and DNA methylases (Rowe et al. 2010, Rowe et al. 2013). DNA methylation and H3K9 trimethylation regulate distinct sets of loci in mouse embryonic stem cells (Karimi et al. 2011). Heterochromatin initiated by a KRAB-ZFP can spread across several tens of kilobases (Groner et al. 2010).

Literature References

PubMed ID	Title	Journal	Year
26813693	Characterization of the Enzymatic Activity of SETDB1 and Its 1:1 Complex with ATF7IP Godbole, A, Hermans, W, Wigle, TJ, Copeland, RA, Leland, PA, Gureasko, J, Basavapathruni, A, Riera, TV, Boriack-Sjodin, PA, Porter Scott, M	Biochemistry	2016
11959841	SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins Schultz, DC, Ayyanathan, K, Maul, GG, Rauscher, FJ, Negorev, D	Genes Dev.	2002
14536086	mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression Roeder, RG, An, W, Chatton, B, Zhang, Y, Xia, L, Wang, H, Tempst, P, Cao, R, Erdjument-Bromage, H	Mol. Cell	2003