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Chromatin Remodeling by BRG1 and SNF2H: Biochemistry and Function
Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut för experimentell biologi.
2004 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Chromatin is a highly dynamic, regulatory component in the process of transcription, repair, recombination and replication. The BRG1 and SNF2H proteins are ATP-dependent chromatin remodeling proteins that modulate chromatin structure to regulate DNA accessibility for DNA-binding proteins involved in these processes. The BRG1 protein is a central ATPase of the SWI/SNF complexes involved in chromatin remodeling associated with regulation of transcription. SWI/SNF complexes are biochemically hetero-geneous but little is known about the unique functional characteristics of the various forms. We have shown that SWI/SNF activity in SW13 cells affects actin filament organization dependent on the RhoA signaling pathway. We have further shown that the biochemical composition of SWI/SNF complexes qualitatively affects the remodeling activity and that the composition of biochemically purified SWI/SNF complexes does not reflect the patterns of chromatin binding of individual subunits. Chromatin binding assays (ChIP) reveal variations among subunits believed to be constitutive, suggesting that the plasticity in SWI/SNF complex composition is greater than suspected. We have also discovered an interaction between BRG1 and the splicing factor Prp8, linking SWI/SNF activity to mRNA processing. We propose a model whereby parts of the biochemical heterogeneity is a result of function and that the local chromatin environment to which the complex is recruited affect SWI/SNF composition.

We have also isolated the novel B-WICH complex that contains WSTF, SNF2H, the splicing factor SAP155, the RNA helicase II/Guα, the transcription factor Myb-binding protein 1a, the transcription factor/DNA repair protein CSB and the RNA processing factor DEK. The formation of this complex is dependent on active transcription and links chromatin remodeling by SNF2H to RNA processing.

By linking chromatin remodeling complexes with RNA processing proteins our work has begun to build a bridge between chromatin and RNA, suggesting that factors in chromatin associated assemblies translocate onto the growing nascent RNA.

Ort, förlag, år, upplaga, sidor
Stockholm: Wenner-Grens institut för experimentell biologi , 2004. , s. 61
Nyckelord [en]
chromatin, chromatin remodeling, SWI/SNF, ISWI, BRG1, SNF2H, Prp8, RNA, transcription
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:su:diva-206ISBN: 91-7265-914-9 (tryckt)OAI: oai:DiVA.org:su-206DiVA, id: diva2:190933
Disputation
2004-09-10, De Geersalen, Geovetenskapens hus, Svante Arrhenius väg 8 A, Stockholm, 10:00
Opponent
Handledare
Tillgänglig från: 2004-08-20 Skapad: 2004-08-20Bibliografiskt granskad
Delarbeten
1. Expression of BRG1, a human SWI/SNF component, affects the organisation of actin filaments through the RhoA signalling pathway
Öppna denna publikation i ny flik eller fönster >>Expression of BRG1, a human SWI/SNF component, affects the organisation of actin filaments through the RhoA signalling pathway
2002 (Engelska)Ingår i: Journal of Cell Science, ISSN 0021-9533, Vol. 115, nr 3, s. 2735-2745Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The human BRG1 (brahma-related gene 1) protein is a component of the SWI/SNF family of the ATP-dependent chromatin remodelling complexes. We show here that expression of the BRG1 protein, but not of an ATPase-deficient BRG1 protein, in BRG1-deficient SW13 cells alters the organisation of actin filaments. BRG1 expression induces the formation of thick actin filament bundles resembling stress-fibres, structures that are rarely seen in native SW13 cells. BRG1 expression does not influence the activity state of the RhoA-GTPase, which is involved in stress-fibre formation. We find that RhoA is equally activated by stimuli, such as serum, in BRG1-expressing cells, ATPase-deficient BRG1-expressing cells and native SW13 cells. However, the activation of RhoA by lysophosphatidic acid and serum does not trigger the formation of stress-fibre-like structures in SW13 cells. Activation of the RhoA-GTPase in BRG1-expressing cells induces stress-fibre-like structures, indicating that the BRG1 can couple RhoA activation to stress-fibre formation. At least two downstream effectors are involved in stress-fibre formation, Rho-kinase/ROCK and Dia. BRG1 expression, but not the expression of the ATP-deficient BRG1, increases the protein level of ROCK1, one form of the Rho-kinase/ROCK. That this is of importance is supported by the findings that an increased Rho-kinase/ROCK activity in SW13 cells, obtained by overexpressing wild-type ROCK1 and ROCK2, induces stress-fibre formation. No specificity between the two Rho-kinase/ROCK forms exists. Our results suggest that the BRG1 protein affects the RhoA pathway by increasing the protein level of ROCK1, which allows stress-fibre-like structures to form.

Ort, förlag, år, upplaga, sidor
Company of Biologists Ltd., 2002
Nyckelord
BRG1; SWI/SNF; actin filament organisation; RhoA; Rho kinases
Identifikatorer
urn:nbn:se:su:diva-23252 (URN)
Anmärkning
Part of urn:nbn:se:su:diva-206Tillgänglig från: 2004-08-20 Skapad: 2004-08-20 Senast uppdaterad: 2010-01-05Bibliografiskt granskad
2. Variations in subunit composition and chromatin association of mammalian SWI/SNF complexes
Öppna denna publikation i ny flik eller fönster >>Variations in subunit composition and chromatin association of mammalian SWI/SNF complexes
Manuskript (Övrigt vetenskapligt)
Identifikatorer
urn:nbn:se:su:diva-23253 (URN)
Anmärkning
Part of urn:nbn:se:su:diva-206Tillgänglig från: 2004-08-20 Skapad: 2004-08-20 Senast uppdaterad: 2010-01-13Bibliografiskt granskad
3. WSTF-SNF2h interacts ith several nuclear proteins in a transcription dependent manner, to form a functional unit B-WICH
Öppna denna publikation i ny flik eller fönster >>WSTF-SNF2h interacts ith several nuclear proteins in a transcription dependent manner, to form a functional unit B-WICH
Manuskript (Övrigt vetenskapligt)
Identifikatorer
urn:nbn:se:su:diva-23254 (URN)
Anmärkning
Part of urn:nbn:se:su:diva-206Tillgänglig från: 2004-08-20 Skapad: 2004-08-20 Senast uppdaterad: 2010-01-13Bibliografiskt granskad

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