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 |
_c2257 _d2257 |