News update via NF Bot

Read the full paper: Structural basis of a SWI/SNF-associated transcription pre-initiation complex

The SWI/SNF chromatin remodeling subunit ARID1B is subjected to proteasomal degradation through K27/K29-linked polyubiquitination mediated by the HECT E3 ubiquitin ligase WWP2. Using cancer cell line...

Cryo-EM and genetic analyses reveal that the SWI/SNF chromatin remodeler is an integral component of the transcription pre-initiation complex. The structures demonstrate how SWI/SNF facilitates transcription initiation through stabilization of PIC organization and concerted remodeling of the +1 nucleosome.

Read the full paper: The Drosophila SWI/SNF complex subunit Bap60 is required for training-induced gene transcription during long-term memory formation

Urothelial cancer (UC) cells of the luminal subtype exhibit partial, incomplete differentiation towards umbrella cells that line bladder lumen, seen by morphology and gene expression. Differentiation is stalled even though the cells express master transcription factors (MTFs) that drive luminal urothelial differentiation, e.g., FOXA1 and CEBPB, at levels seen in normal differentiated urothelium. We therefore analyzed the FOXA1/CEBPB MTF hub by mass spectrometry. SWI/SNF coactivator complex (CoA) components, e.g., SMARCA4, ARID1A, that read the epigenetic activation mark histone 3 lysine 27 acetylation (H3K27ac) and use ATP-hydrolysis to open chromatin, were the most abundant proteins pulled-down with FOXA1/CEBPB. However, genes for these and other CoA, e.g., CREBBP, EP300 that write H3K27ac, were mutated/deleted in >95% of UCs in clinical series. Also contained in the hub were corepressors (CoR) that erase H3K27ac and close chromatin, e.g., HDAC1, CHD4; genes for these CoR were recurrently gained in UCs. Chromatin analyses showed H3K27ac-centered remodeling was needed to activate umbrella but not constitutively accessible cell growth/division/housekeeping genes. Restoring ARID1A into ARID1A-mutated UC cells using lentiviral transduction, or inhibiting CoR with siRNA or small molecules, activated umbrella genes and terminated replications. In summary, UC-genesis selects for loss- and gain-of-function of CoA and CoR respectively in the urothelial-lineage MTF hub; small molecule CoR-inhibitors are candidate remedies to renew maturation towards terminal differentiated-fates.

Abstract The Bap170 subunit of the SWI/SNF chromatin remodeler exhibits activator functions when artificially recruited to the LacZ reporter promoter in enhancer-dependent transcription. In this study...

PubMed link

DNA double-strand break (DSB) repair pathway choice is strongly influenced by DNA end resection, a process in which the 5′ DNA strand is degraded to generate 3′ single-stranded DNA required for homolo...