ATP chromatin remodelling
Cells have multiple remodelling complexes, most of which are multisubunit complexes. Remodelling complexes are grouped into 4 families; INO80, SWI/SNF, CHD and ISWI.Cite error: Invalid
name cannot be a simple integer. Use a descriptive title. Although the different families 'slide, evict and edit'. nucleosomes, ATP hydrolysis drives DNA translocation of the motor domains of these complexes.
ATP depedant chromatin remodelling involves:
- unwrapping nucleosomes
- histone variant exchange
The first complex isolated was SWI/SNF in yeast, with the catalytic subunit being identified as SNF2.
In humans, 3 homologues of SWI/SNF proteins have been identified; hbrm and BRG1, which are homologous of SNF2/SWI2 and hSNF5, which is a homologue of SNF5. Hbrm and BRG1 promote transcriptional activation via the glucocorticoid and retonic acid receptors. BRG1 has been found to activate or repress nuclear processes (transcription, elongation, DNA replication), using various mechanisms including being assembled with transcriptional promoters and histone-modifying enzyme complexes.
As SWI/SNF plays a key role in the cell cycle, it has been indicated to be a potent tumour suppressor. Mutations within subunits of these complexes have been linked to more than 20% of human cancers. " The cancers with the highest SWI/SNF mutation rates were ovarian clear cell carcinoma (75%), clear cell renal cell carcinoma (57%), hepatocellular carcinoma (40%), gastric cancer (36%), melanoma (34%), and pancreatic cancer (26%)". Common mutations within the subunits found to lead to cancer include epigenic silencing, rearrangement and deletions which lead to inactivation of SWI/SNF subunit(s).
ATP dependant complexes work synergestically with HAT complexes; as HAT and ATP-dependant complexes are commonly recruited to the same promoters, which results in a cascade of reactions leading to enhanced production of the pre-initiation complex.
- ↑ Trotter KW, Archer TK. The BRG1 transcriptional coregulator. Nuclear Receptor Signaling. 2008;6(1).
- ↑ S. Eustermann, K.Schall, D.Kostrewa, K. Lakomek, M. Strauss, M. Moldt, K-P. Hopfner. Structural Basis for nucleosome remodelling by the INO80 complex. Nature 2018; 556(7701).
- ↑ S.Whitehall. CMB2001, lecture 4. 2018.
- ↑ Muchardt C, Reyes JC, Bourachot B, Leguoy E, Yaniv M. The hbrm and BRG-1 proteins, components of the human SNF/SWI complex, are phosphorylated and excluded from the condensed chromosomes during mitosis. The EMBO Journal. 1996;15(13):3394–402.
- ↑ S.Whitehall. CMB2001, Lecture 4. 2018
- ↑ Shain AH, Pollack JR. The Spectrum of SWI/SNF Mutations, Ubiquitous in Human Cancers. PLoS ONE. 2013;8(1)
- ↑ Shain AH, Pollack JR. The Spectrum of SWI/SNF Mutations, Ubiquitous in Human Cancers. PLoS ONE. 2013;8(1).
- ↑ S.WHitehall. CMB2001, lecture 4. 2018.