Journal article
Genome-wide binding and mechanistic analyses of Smchd1-mediated epigenetic regulation
K Chen, J Hu, DL Moore, R Liu, SA Kessans, K Breslin, IS Lucet, A Keniry, HS Leong, CL Parish, DJ Hilton, RJLF Lemmers, SM Van Der Maarel, PE Czabotar, RCJ Dobson, ME Ritchie, GF Kay, JM Murphy, ME Blewitt
Proceedings of the National Academy of Sciences of the United States of America | Published : 2015
Abstract
Structural maintenance of chromosomes flexible hinge domain containing 1 (Smchd1) is an epigenetic repressor with described roles in X inactivation and genomic imprinting, but Smchd1 is also critically involved in the pathogenesis of facioscapulohumeral dystrophy. The underlying molecular mechanism by which Smchd1 functions in these instances remains unknown. Our genome-wide transcriptional and epigenetic analyses show that Smchd1 binds cis-regulatory elements, many of which coincide with CCCTC-binding factor (Ctcf) binding sites, for example, the clustered protocadherin (Pcdh) genes, where we show Smchd1 and Ctcf act in opposing ways. We provide biochemical and biophysical evidence that Smc..
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Funding Acknowledgements
We thank Aliaksei Holik for technical assistance. We thank The Dyson Bequest and The DHB Foundation for philanthropic funding (to M.E.B.). This work was supported by grants from the Australian National Health and Medical Research Council (Grant APP1045936 to M.E.B., J.M.M., and M.E.R. and Grant APP1020871 to G.F.K. and M.E.B.). M.E.B. is a Queen Elizabeth II Fellow of the Australian Research Council (DP1096092), and J.M.M. is an Australian Research Council Future Fellow (FT100100100). C.L.P. was supported by a Senior Medical Research Fellowship provided by the Viertel Charitable Foundation, Australia. 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.