Phase separation of Polycomb-repressive complex 1 is governed by a charged disordered region of CBX2

Genes and Development - Tập 33 Số 13-14 - Trang 799-813 - 2019
Aaron J. Plys1,2, Christopher P. Davis1,2, Jongmin Kim1,2, Gizem Rizki3, Madeline M. Keenen4, Sharon K. Marr1, Robert E. Kingston1,2
11Department of Molecular Biology, Massachusetts General Hospital Research Institute, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
22Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
33Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA
44Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94158, USA

Tóm tắt

Mammalian development requires effective mechanisms to repress genes whose expression would generate inappropriately specified cells. The Polycomb-repressive complex 1 (PRC1) family complexes are central to maintaining this repression. These include a set of canonical PRC1 complexes, each of which contains four core proteins, including one from the CBX family. These complexes have been shown previously to reside in membraneless organelles called Polycomb bodies, leading to speculation that canonical PRC1 might be found in a separate phase from the rest of the nucleus. We show here that reconstituted PRC1 readily phase-separates into droplets in vitro at low concentrations and physiological salt conditions. This behavior is driven by the CBX2 subunit. Point mutations in an internal domain of Cbx2 eliminate phase separation. These same point mutations eliminate the formation of puncta in cells and have been shown previously to eliminate nucleosome compaction in vitro and generate axial patterning defects in mice. Thus, the domain of CBX2 that is important for phase separation is the same domain shown previously to be important for chromatin compaction and proper development, raising the possibility of a mechanistic or evolutionary link between these activities.

Từ khóa


Tài liệu tham khảo

10.1002/0471142727.mb1201s75

10.1016/j.cell.2016.06.010

10.1038/nbt1240

10.1128/MCB.26.7.2560-2569.2006

10.1038/s41594-018-0112-y

10.1083/jcb.201308087

10.1126/science.aar4199

10.1126/science.aar2555

10.1038/nsmb.2669

10.1016/1044-0305(94)80016-2

10.1016/j.molcel.2010.02.032

10.1126/science.1100576

10.1016/j.molcel.2012.01.002

10.1101/gad.17288211

10.1146/annurev-cellbio-100913-013325

10.1101/gad.268151.115

10.1016/j.devcel.2013.08.016

10.1093/jb/mvx040

10.1016/j.molcel.2017.01.009

10.1016/j.cell.2013.10.033

10.1038/nature22822

10.1126/science.aah5403

2001, Assembly of nucleosomal templates by salt dialysis, Curr Protoc Mol Biol, 54, 21.6.1

10.1016/j.cell.2016.10.003

10.1038/s41586-018-0174-3

10.15252/embj.201696394

10.1016/j.stem.2011.12.006

10.1002/jms.229

10.1186/1471-2105-7-208

10.1074/jbc.M116.730853

10.1128/MCB.00949-07

10.1016/S0168-9525(00)02024-2

10.1126/science.aar3958

10.1128/MCB.17.7.4105

10.1083/jcb.142.4.887

10.1002/0471142727.mb2105s50

10.1016/j.celrep.2013.11.017

10.1016/j.molcel.2008.10.016

10.1021/ac950914h

10.1126/science.aaf4382

10.1016/j.molcel.2013.02.013

10.1016/j.cell.2006.12.041

10.1038/nature22989

10.1016/j.molcel.2015.02.013

10.1074/jbc.RA118.006620

10.1038/28886

10.1016/j.cell.2018.06.006

10.1038/ncomms10291

10.1126/science.1068539

10.1091/mbc.E14-06-1109

Thông tin
Thông tin xuất bản

Genes and Development

Tập 33 Số 13-14

799-813

Thông tin tác giả