Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters
Natasha Jansz, Andrew Keniry, Marie Trussart, Heidi Bildsoe, Tamara Beck, Ian D Tonks, Arne W Mould, Peter Hickey, Kelsey Breslin, Megan Iminitoff, Matthew E Ritchie, Edwina McGlinn, Graham F Kay, James M Murphy, Marnie E Blewitt
NATURE STRUCTURAL & MOLECULAR BIOLOGY | NATURE PUBLISHING GROUP | Published : 2018
The regulation of higher-order chromatin structure is complex and dynamic, and a full understanding of the suite of mechanisms governing this architecture is lacking. Here, we reveal the noncanonical SMC protein Smchd1 to be a novel regulator of long-range chromatin interactions in mice, and we add Smchd1 to the canon of epigenetic proteins required for Hox-gene regulation. The effect of losing Smchd1-dependent chromatin interactions has varying outcomes that depend on chromatin context. At autosomal targets transcriptionally sensitive to Smchd1 deletion, we found increased short-range interactions and ectopic enhancer activation. In contrast, the inactive X chromosome was transcriptionally ..View full abstract
Awarded by Australian National Health and Medical Research Council
We thank H. Coughlin, R. Allan and T. Johansson for useful discussions. This work was funded by an Australian National Health and Medical Research Council grant to M.E.B., J.M.M. and M.E.R. (GNT1098290), and fellowships to J.M.M. (GNT1105754) and M.E.R. (GNT1104924). N.J. was supported by an Australian Research Training Program Fellowship. M.E.B. was supported by a Bellberry-Viertel Senior Medical Research Fellowship. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. This work was made possible through Victorian State Government Operational Infrastructure Support and the Australian National Health and Medical Research Council Research Institute Infrastructure Support Scheme.