000 02797 am a22003973u 4500
042 _adc
100 1 0 _aSchick, Sandra
_eauthor
_92358
700 1 0 _aGrosche, Sarah
_eauthor
_92359
700 1 0 _aKohl, Katharina Eva
_eauthor
_92360
700 1 0 _aDrpic, Danica
_eauthor
_92361
700 1 0 _aJaeger, Martin G.
_eauthor
_92362
700 1 0 _aMarella, Nara C.
_eauthor
_92363
700 1 0 _aImrichova, Hana
_eauthor
_92364
700 1 0 _aLin, Jung-Ming G.
_eauthor
_92365
700 1 0 _aHofstätter, Gerald
_eauthor
_92366
700 1 0 _aSchuster, Michael
_eauthor
_92367
700 1 0 _aRendeiro, André F.
_eauthor
_92368
700 1 0 _aKoren, Anna
_eauthor
_92369
700 1 0 _aPetronczki, Mark
_eauthor
_92370
700 1 0 _aBock, Christoph
_eauthor
_92371
700 1 0 _aMüller, André C.
_eauthor
_92372
700 1 0 _aWinter, Georg E.
_eauthor
_92373
700 1 0 _aKubicek, Stefan
_eauthor
_92374
245 0 0 _aAcute BAF perturbation causes immediate changes in chromatin accessibility
260 _c2021-03-01.
500 _a/pmc/articles/PMC7614082/
500 _a/pubmed/33558760
520 _aCancer-associated loss-of-function mutations in genes coding for subunits of the BRG1/BRM associated factor (BAF) chromatin remodeling complexes(1-8) often cause drastic chromatin accessibility changes, especially in important regulatory regions(9-19). However, it remains unknown how these changes are established over time (e.g. immediate consequences or long-term adaptations), and whether they are causative for intra-complex synthetic lethalities abrogating the formation or activity of BAF complexes(9,20-24). Here, we use the dTAG system to induce acute degradation of BAF subunits and show that chromatin alterations are established faster than the duration of one cell cycle. Using a pharmacological inhibitor and a chemical degrader of the BAF complex ATPase subunits(25,26), we show that maintaining genome accessibility requires constant ATP-dependent remodeling. Completely abolishing BAF complex function by acute degradation of a synthetic lethal subunit in a paralog-deficient background results in a near-complete loss of chromatin accessibility at BAF-controlled sites, especially at super-enhancers, providing a mechanism for intra-complex synthetic lethalities.
540 _a
540 _ahttp://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nNat Genet
856 4 1 _uhttp://dx.doi.org/10.1038/s41588-021-00777-3
_zConnect to this object online.
999 _c2097
_d2097