ATF7IP-Mediated Stabilization of the Histone Methyltransferase SETDB1 Is Essential for Heterochromatin Formation by the HUSH Complex
Elsevier (Cell Press)
MetadataShow full item record
Timms, R., Tchasovnikarova, I., Antrobus, R., Dougan, G., & Lehner, P. (2016). ATF7IP-Mediated Stabilization of the Histone Methyltransferase SETDB1 Is Essential for Heterochromatin Formation by the HUSH Complex. Cell Reports, 17 653-659. https://doi.org/10.1016/j.celrep.2016.09.050
The histone methyltransferase SETDB1 plays a central role in repressive chromatin processes, but the functional requirement for its binding partner ATF7IP has remained enigmatic. Here, we show that ATF7IP is essential for SETDB1 stability: nuclear SETDB1 protein is degraded by the proteasome upon ablation of ATF7IP. As a result, ATF7IP is critical for repression that requires H3K9 trimethylation by SETDB1, including transgene silencing by the HUSH complex. Furthermore, we show that loss of ATF7IP phenocopies loss of SETDB1 in genome-wide assays. ATF7IP and SETDB1 knockout cells exhibit near-identical defects in the global deposition of H3K9me3, which results in similar dysregulation of the transcriptome. Overall, these data identify a critical functional role for ATF7IP in heterochromatin formation by regulating SETDB1 abundance in the nucleus.
heterochromatin, epigenetic silencing, histone methylation, H3K9me3, SETDB1, HUSH complex, ATF7IP, ubiquitin-mediated degradation
This work was supported by the Wellcome Trust through a Principal Research Fellowship to P.J.L. (101835/Z/13/Z) and a Ph.D. studentship to I.A.T. The CIMR is in receipt of a Wellcome Trust strategic award.
Wellcome Trust (101835/Z/13/Z)
Embargo Lift Date
External DOI: https://doi.org/10.1016/j.celrep.2016.09.050
This record's URL: https://www.repository.cam.ac.uk/handle/1810/261085
Recommended or similar items
The following licence files are associated with this item: