scholarly journals Differential Targeting of Two Distinct SWI/SNF-Related Drosophila Chromatin-Remodeling Complexes

2004 ◽  
Vol 24 (8) ◽  
pp. 3077-3088 ◽  
Author(s):  
Lisette Mohrmann ◽  
Karin Langenberg ◽  
Jeroen Krijgsveld ◽  
Arnoud J. Kal ◽  
Albert J. R. Heck ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Polytene Chromosomes ◽  
Distribution Patterns ◽  
Human Cells ◽  
Genome Wide ◽  
Larval Salivary Gland ◽  
Associated Proteins ◽  
Chromatin Remodeling Complexes ◽  
Distinct Distribution

ABSTRACT The SWI/SNF family of ATP-dependent chromatin-remodeling factors plays a central role in eukaryotic transcriptional regulation. In yeast and human cells, two subclasses have been recognized: one comprises yeast SWI/SNF and human BAF, and the other includes yeast RSC and human PBAF. Therefore, it was puzzling that Drosophila appeared to contain only a single SWI/SNF-type remodeler, the Brahma (BRM) complex. Here, we report the identification of two novel BRM complex-associated proteins: Drosophila Polybromo and BAP170, a conserved protein not described previously. Biochemical analysis established that Drosophila contains two distinct BRM complexes: (i) the BAP complex, defined by the presence of OSA and the absence of Polybromo and BAP170, and (ii) the PBAP complex, containing Polybromo and BAP170 but lacking OSA. Determination of the genome-wide distributions of OSA and Polybromo on larval salivary gland polytene chromosomes revealed that BAP and PBAP display overlapping but distinct distribution patterns. Both complexes associate predominantly with regions of open, hyperacetylated chromatin but are largely excluded from Polycomb-bound repressive chromatin. We conclude that, like yeast and human cells, Drosophila cells express two distinct subclasses of the SWI/SNF family. Our results support a close reciprocity of chromatin regulation by ATP-dependent remodelers and histone-modifying enzymes.

scholarly journals The Transcriptional Coactivator SAYP Is a Trithorax Group Signature Subunit of the PBAP Chromatin Remodeling Complex

2008 ◽  
Vol 28 (9) ◽  
pp. 2920-2929 ◽  
Author(s):  
Gillian E. Chalkley ◽  
Yuri M. Moshkin ◽  
Karin Langenberg ◽  
Karel Bezstarosti ◽  
Andras Blastyak ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Polytene Chromosomes ◽  
Group Signature ◽  
Transcriptional Coactivator ◽  
Trithorax Group ◽  
Phd Finger ◽  
Gene Expression Control ◽  
Larval Salivary Gland ◽  
Eukaryotic Gene ◽  
Chromatin Remodeling Complexes

ABSTRACT SWI/SNF ATP-dependent chromatin remodeling complexes (remodelers) perform critical functions in eukaryotic gene expression control. BAP and PBAP are the fly representatives of the two evolutionarily conserved major subclasses of SWI/SNF remodelers. Both complexes share seven core subunits, including the Brahma ATPase, but differ in a few signature subunits; POLYBROMO and BAP170 specify PBAP, whereas OSA defines BAP. Here, we show that the transcriptional coactivator and PHD finger protein SAYP is a novel PBAP subunit. Biochemical analysis established that SAYP is tightly associated with PBAP but absent from BAP. SAYP, POLYBROMO, and BAP170 display an intimately overlapping distribution on larval salivary gland polytene chromosomes. Genome-wide expression analysis revealed that SAYP is critical for PBAP-dependent transcription. SAYP is required for normal development and interacts genetically with core- and PBAP-selective subunits. Genetic analysis suggested that, like BAP, PBAP also counteracts Polycomb silencing. SAYP appears to be a key architectural component required for the integrity and association of the PBAP-specific module. We conclude that SAYP is a signature subunit that plays a major role in the functional specificity of the PBAP holoenzyme.

Chromatin remodeling complexes: ATP-dependent machines in action

2005 ◽  
Vol 83 (4) ◽  
pp. 405-417 ◽  
Author(s):  
Cotteka N Johnson ◽  
Nicholas L Adkins ◽  
Philippe Georgel
Keyword(s):  
Chromatin Remodeling ◽  
Atp Hydrolysis ◽  
Nucleosome Remodeling ◽  
Core Histones ◽  
Associated Proteins ◽  
Chromatin Template ◽  
Chromatin Remodeling Complexes ◽  
The Individual ◽  
Insight Into

Since the initial characterization of chromatin remodeling as an ATP-dependent process, many studies have given us insight into how nucleosome-remodeling complexes can affect various nuclear functions. However, the multistep DNA-histone remodeling process has not been completely elucidated. Although new studies are published on a nearly weekly basis, the nature and roles of interactions of the individual SWI/SNF- and ISWI-based remodeling complexes and DNA, core histones, and other chromatin-associated proteins are not fully understood. In addition, the potential changes associated with ATP recruitment and its subsequent hydrolysis have not been fully characterized. This review explores possible mechanisms by which chromatin-remodeling complexes are recruited to specific loci, use ATP hydrolysis to achieve actual remodeling through disruption of DNA-histone interactions, and are released from their chromatin template. We propose possible roles for ATP hydrolysis in a chromatin-release/target-scanning process that offer an alternative to or complement the often overlooked function of delivering the energy required for sliding or dislodging specific subsets of core histones.Key words: chromatin remodeling, SWI/SNF, ISWI, APT hydrolysis.

scholarly journals Activation of the ADE Genes Requires the Chromatin Remodeling Complexes SAGA and SWI/SNF

2007 ◽  
Vol 6 (8) ◽  
pp. 1474-1485 ◽  
Author(s):  
Rebecca N. Koehler ◽  
Nicole Rachfall ◽  
Ronda J. Rolfes
Keyword(s):  
Chromatin Remodeling ◽  
Growth Conditions ◽  
Specific Response ◽  
Wild Type ◽  
Reporter Expression ◽  
Activator Proteins ◽  
Genome Wide ◽  
A Genome ◽  
Chromatin Remodeling Complexes ◽  
Type Strains

ABSTRACT The activation of the ADE regulon genes requires the pair of transcription factors Bas1 and Pho2. In a genome-wide screen for additional regulators of the pathway, strains with mutations in multiple subunits of the chromatin remodeling complexes SAGA and SWI/SNF were uncovered. These mutants exhibited decreased expression of an ADE5,7-lacZ reporter and native ADE compared to the wild-type strains, but the expression of the BAS1 and PHO2 genes was not substantially decreased. An unregulated Bas1-Pho2 fusion protein depended upon SAGA and SWI/SNF activity to promote transcription of a reporter. A significant but low-level association of Gcn5-myc and Snf2-myc with the ADE5,7 promoter was independent of adenine growth conditions and independent of the presence of the activator proteins Bas1 and Pho2. However, the increase in occupancy of Bas1 and Pho2 at ADE5,7 depended on both SAGA and SWI/SNF. The loss of catalytic activity of both SAGA and SWI/SNF complexes in the gcn5Δ snf2Δ double mutant was severely detrimental to ADE-lacZ reporter expression and native ADE gene expression, indicating complementary roles for these complexes. We conclude that Bas1 and Pho2 do not recruit the SAGA and SWI/SNF complexes to the ADE5,7 promoter but that the remodeling complexes are necessary to increase the binding of Bas1 and Pho2 in response to the adenine regulatory signal. Our data support the model that the SAGA and SWI/SNF complexes engage in global surveillance that is necessary for the specific response by Bas1 and Pho2.

scholarly journals Yeast Isw1p Forms Two Separable Complexes In Vivo

2003 ◽  
Vol 23 (1) ◽  
pp. 80-91 ◽  
Author(s):  
Jay C. Vary, ◽  
Vamsi K. Gangaraju ◽  
Jun Qin ◽  
Carolyn Church Landel ◽  
Charles Kooperberg ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcriptional Regulation ◽  
Chromatin Remodeling ◽  
Elevated Temperatures ◽  
Cellular Processes ◽  
Biochemical Assays ◽  
Associated Proteins ◽  
Chromatin Remodeling Complexes ◽  
Specific Activities

ABSTRACT There are several classes of ATP-dependent chromatin remodeling complexes, which modulate the structure of chromatin to regulate a variety of cellular processes. The budding yeast, Saccharomyces cerevisiae, encodes two ATPases of the ISWI class, Isw1p and Isw2p. Previously Isw1p was shown to copurify with three other proteins. Here we identify these associated proteins and show that Isw1p forms two separable complexes in vivo (designated Isw1a and Isw1b). Biochemical assays revealed that while both have equivalent nucleosome-stimulated ATPase activities, Isw1a and Isw1b differ in their abilities to bind to DNA and nucleosomal substrates, which possibly accounts for differences in specific activities in nucleosomal spacing and sliding. In vivo, the two Isw1 complexes have overlapping functions in transcriptional regulation of some genes yet distinct functions at others. In addition, these complexes show different contributions to cell growth at elevated temperatures.

scholarly journals Genome-wide Association of Yorkie with Chromatin and Chromatin-Remodeling Complexes

Cell Reports ◽  
2013 ◽  
Vol 3 (2) ◽  
pp. 309-318 ◽  
Author(s):  
Hyangyee Oh ◽  
Matthew Slattery ◽  
Lijia Ma ◽  
Alex Crofts ◽  
Kevin P. White ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Chromatin Remodeling Complexes

scholarly journals In-Depth Characterization and Validation in BRG1-Mutant Lung Cancers Define Novel Catalytic Inhibitors of SWI/SNF Chromatin Remodeling

2019 ◽  
Author(s):  
Zainab Jagani ◽  
Gregg Chenail ◽  
Kay Xiang ◽  
Geoffrey Bushold ◽  
Hyo-Eun C. Bhang ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Therapeutic Potential ◽  
Synthetic Lethality ◽  
Critical Role ◽  
Chromatin Accessibility ◽  
Lung Cancers ◽  
Catalytic Function ◽  
Genome Wide ◽  
Chromatin Remodeling Complexes ◽  
Chromatin Profiling

AbstractMembers of the ATP-dependent SWI/SNF chromatin remodeling complexes are among the most frequently mutated genes in cancer, suggesting their dysregulation plays a critical role. The synthetic lethality between SWI/SNF catalytic subunits BRM/SMARCA2 and BRG1/SMARCA4 has instigated great interest in targeting BRM. Here we have performed a critical and in-depth investigation of novel dual inhibitors (BRM011 and BRM014) of BRM and BRG1 in order to validate their utility as chemical probes of SWI/SNF catalytic function, while obtaining insights into the therapeutic potential of SWI/SNF inhibition. In corroboration of on-target activity, we discovered compound resistant mutations through pooled screening of BRM variants in BRG1-mut cancer cells. Strikingly, genome-wide transcriptional and chromatin profiling (ATAC-Seq) provided further evidence of pharmacological perturbation of SWI/SNF chromatin remodeling as BRM011 treatment induced specific changes in chromatin accessibility and gene expression similar to genetic depletion of BRM. Finally, these compounds have the capacity to inhibit the growth of tumor-xenografts, yielding important insights into the feasibility of developing BRM/BRG1 ATPase inhibitors for the treatment of BRG1-mut lung cancers. Overall, our studies not only establish the feasibility of inhibiting SWI/SNF catalytic function, providing a framework for SWI/SNF therapeutic targeting, but have also yielded successful elucidation of small-molecule inhibitors that will be of importance in probing SWI/SNF function in various disease contexts.

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