Journal article

SMCHD1's ubiquitin-like domain is required for N-terminal dimerization and chromatin localization

Alexandra D Gurzau, Christopher R Horne, Yee-Foong Mok, Megan Iminitoff, Tracy A Willson, Samuel N Young, Marnie E Blewitt, James M Murphy

BIOCHEMICAL JOURNAL | PORTLAND PRESS LTD | Published : 2021

Abstract

Structural maintenance of chromosomes flexible hinge domain-containing 1 (SMCHD1) is an epigenetic regulator that mediates gene expression silencing at targeted sites across the genome. Our current understanding of SMCHD1's molecular mechanism, and how substitutions within SMCHD1 lead to the diseases, facioscapulohumeral muscular dystrophy (FSHD) and Bosma arhinia microphthalmia syndrome (BAMS), are only emerging. Recent structural studies of its two component domains - the N-terminal ATPase and C-terminal SMC hinge - suggest that dimerization of each domain plays a central role in SMCHD1 function. Here, using biophysical techniques, we demonstrate that the SMCHD1 ATPase undergoes dimerizati..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by FSHD Global


Awarded by FSHD Society Fellowship


Funding Acknowledgements

This work was supported by grants from the National Health and Medical Research Council of Australia (1098290, 1172929, 1194345, 9000653) and FSHD Global (grant 39); Australian Research Training Program scholarships to A.D.G. and M.I.; an FSHD Society Fellowship (5059384059) to A.D.G; the Bellberry-Viertel Senior Medical Research Fellowship (to M.E.B). Additional support was provided by the Victorian State Government Operational Infrastructure Support.