TY  - BOOK
AU  - Schick,Sandra
AU  - Grosche,Sarah
AU  - Kohl,Katharina Eva
AU  - Drpic,Danica
AU  - Jaeger,Martin G.
AU  - Marella,Nara C.
AU  - Imrichova,Hana
AU  - Lin,Jung-Ming G.
AU  - Hofstätter,Gerald
AU  - Schuster,Michael
AU  - Rendeiro,André F.
AU  - Koren,Anna
AU  - Petronczki,Mark
AU  - Bock,Christoph
AU  - Müller,André C.
AU  - Winter,Georg E.
AU  - Kubicek,Stefan
TI  - Acute BAF perturbation causes immediate changes in chromatin accessibility
PY  - 2021///-03-01
KW  - Text
KW  - local
N1  - /pmc/articles/PMC7614082; /pubmed/33558760
N2  - Cancer-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
UR  - http://dx.doi.org/10.1038/s41588-021-00777-3
ER  -