The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin

Julia Truch, Damien J. Downes, Caroline Scott, E. Ravza Gür, Jelena M. Telenius, Emmanouela Repapi, Ron Schwessinger, Matthew Gosden, Jill M. Brown, Stephen Taylor, Pak Leng Cheong, Jim R. Hughes, Douglas R. Higgs () and Richard J. Gibbons ()
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Julia Truch: University of Oxford
Damien J. Downes: University of Oxford
Caroline Scott: University of Oxford
E. Ravza Gür: University of Oxford
Jelena M. Telenius: University of Oxford
Emmanouela Repapi: University of Oxford
Ron Schwessinger: University of Oxford
Matthew Gosden: University of Oxford
Jill M. Brown: University of Oxford
Stephen Taylor: University of Oxford
Pak Leng Cheong: University of Oxford
Jim R. Hughes: University of Oxford
Douglas R. Higgs: University of Oxford
Richard J. Gibbons: University of Oxford

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract The chromatin remodeller ATRX interacts with the histone chaperone DAXX to deposit the histone variant H3.3 at sites of nucleosome turnover. ATRX is known to bind repetitive, heterochromatic regions of the genome including telomeres, ribosomal DNA and pericentric repeats, many of which are putative G-quadruplex forming sequences (PQS). At these sites ATRX plays an ancillary role in a wide range of nuclear processes facilitating replication, chromatin modification and transcription. Here, using an improved protocol for chromatin immunoprecipitation, we show that ATRX also binds active regulatory elements in euchromatin. Mutations in ATRX lead to perturbation of gene expression associated with a reduction in chromatin accessibility, histone modification, transcription factor binding and deposition of H3.3 at the sequences to which it normally binds. In erythroid cells where downregulation of α-globin expression is a hallmark of ATR-X syndrome, perturbation of chromatin accessibility and gene expression occurs in only a subset of cells. The stochastic nature of this process suggests that ATRX acts as a general facilitator of cell specific transcriptional and epigenetic programmes, both in heterochromatin and euchromatin.

Date: 2022
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DOI: 10.1038/s41467-022-31194-7

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