Position-effect variegation revisited: HUSHing up heterochromatin in human cells
Publication Date
2016-02-08Journal Title
BioEssays
ISSN
0265-9247
Publisher
Wiley
Volume
38
Pages
333-343
Language
English
Type
Article
Metadata
Show full item recordCitation
Timms, R., Tchasovnikarova, I., & Lehner, P. (2016). Position-effect variegation revisited: HUSHing up heterochromatin in human cells. BioEssays, 38 333-343. https://doi.org/10.1002/bies.201500184
Abstract
Much of what we understand about heterochromatin formation in mammals has been extrapolated from forward genetic screens for modifiers of position-effect variegation (PEV) in the fruit fly Drosophila melanogaster. The recent identification of the HUSH (Human Silencing Hub) complex suggests that more recent evolutionary developments contribute to the mechanisms underlying PEV in human cells. Although HUSH-mediated repression also involves heterochromatin spreading through the reading and writing of the repressive H3K9me3 histone modification, clear orthologues of HUSH subunits are not found in Drosophila but are conserved in vertebrates. Here we compare the insights into the mechanisms of PEV derived from genetic screens in the fly, the mouse and in human cells, review what is currently known about the HUSH complex, and discuss the implications of HUSH-mediated silencing for viral latency. Future studies will provide mechanistic insight into HUSH complex function and reveal the relationship between HUSH and other epigenetic silencing complexes.
Sponsorship
This work was funded by a Wellcome Trust Principal Research Fellowship to P.J.L. (084957/Z/08/Z) and a Wellcome Trust PhD studentship to I.A.T. The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award.
Funder references
Wellcome Trust (101835/Z/13/Z)
Wellcome Trust (084957/Z/08/Z)
Identifiers
External DOI: https://doi.org/10.1002/bies.201500184
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253584
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