Document Type
Article
Publication Date
11-5-2022
Publication Title
Nature Communications
Volume
13
First page number:
1
Last page number:
16
Abstract
The assembly of mammalian SWI/SNF chromatin remodeling complexes is developmentally programed, and loss/mutations of SWI/SNF subunits alter the levels of other components through proteolysis, causing cancers. Here, we show that mouse Lsd1/Kdm1a deletion causes dramatic dissolution of SWI/SNF complexes and that LSD1 demethylates the methylated lysine residues in SMARCC1 and SMARCC2 to preserve the structural integrity of SWI/SNF complexes. The methylated SMARCC1/SMARCC2 are targeted for proteolysis by L3MBTL3 and the CRL4DCAF5 ubiquitin ligase complex. We identify SMARCC1 as the critical target of LSD1 and L3MBTL3 to maintain the pluripotency and self-renewal of embryonic stem cells. L3MBTL3 also regulates SMARCC1/SMARCC2 proteolysis induced by the loss of SWI/SNF subunits. Consistently, mouse L3mbtl3 deletion causes striking accumulation of SWI/SNF components, associated with embryonic lethality. Our studies reveal that the assembly/disassembly of SWI/SNF complexes is dynamically controlled by a lysine-methylation dependent proteolytic mechanism to maintain the integrity of the SWI/SNF complexes.
Controlled Subject
Chromatin; Mammals; Biocomplexity
Disciplines
Biochemistry | Chemistry
File Format
File Size
3400 KB
Language
English
Rights
IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Repository Citation
Guo, P.,
Hoang, N.,
Sanchez, J.,
Zhang, E. H.,
Rajawasam, K.,
Trinidad, K.,
Sun, H.,
Zhang, H.
(2022).
The Assembly of Mammalian SWI/SNFChromatin Remodeling Complexes is Regulated by Lysine-Methylation Dependent Proteolysis.
Nature Communications, 13
1-16.
http://dx.doi.org/10.1038/s41467-022-34348-9
