How many remodelers does it take to make a brain? Diverse and cooperative roles of ATP-dependent chromatin-remodeling complexes in developmentThis paper is one of a selection of papers published in this Special Issue, entitled 28th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

2007 ◽  
Vol 85 (4) ◽  
pp. 444-462 ◽  
Author(s):  
Elvin Brown ◽  
Sreepurna Malakar ◽  
Jocelyn E. Krebs

The development of a metazoan from a single-celled zygote to a complex multicellular organism requires elaborate and carefully regulated programs of gene expression. However, the tight packaging of genomic DNA into chromatin makes genes inaccessible to the cellular machinery and must be overcome by the processes of chromatin remodeling; in addition, chromatin remodeling can preferentially silence genes when their expression is not required. One class of chromatin remodelers, ATP-dependent chromatin-remodeling enzymes, can slide nucleosomes along the DNA to make specific DNA sequences accessible or inaccessible to regulators at a particular stage of development. While all ATPases in the SWI2/SNF2 superfamily share the fundamental ability to alter DNA accessibility in chromatin, they do not act alone, but rather, are subunits of a large assortment of protein complexes. Recent studies illuminate common themes by which the subunit compositions of chromatin-remodeling complexes specify the developmental roles that chromatin remodelers play in specific tissues and at specific stages of development, in response to specific signaling pathways and transcription factors. In this review, we will discuss the known roles in metazoan development of 3 major subfamilies of chromatin-remodeling complexes: the SNF2, ISWI, and CHD subfamilies.

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1621 ◽  
Author(s):  
Mohammad Aslam ◽  
Beenish Fakher ◽  
Bello Hassan Jakada ◽  
Shijiang Cao ◽  
Yuan Qin

The nucleosome is the structural and fundamental unit of eukaryotic chromatin. The chromatin remodeling complexes change nucleosome composition, packaging and positioning to regulate DNA accessibility for cellular machinery. SWI2/SNF2-Related 1 Chromatin Remodeling Complex (SWR1-C) belongs to the INO80 chromatin remodeling family and mainly catalyzes the exchange of H2A-H2B with the H2A.Z-H2B dimer. The replacement of H2A.Z into nucleosomes affects nucleosome stability and chromatin structure. Incorporation of H2A.Z into the chromatin and its physiochemical properties play a key role in transcriptional regulation during developmental and environmental responses. In Arabidopsis, various studies have uncovered several pivotal roles of SWR1-C. Recently, notable progress has been achieved in understanding the role of SWR1-C in plant developmental and physiological processes such as DNA damage repair, stress tolerance, and flowering time. The present article introduces the SWR1-C and comprehensively reviews recent discoveries made in understanding the function of the SWR1 complex in plants.


2011 ◽  
Vol 89 (1) ◽  
pp. 12-23 ◽  
Author(s):  
Chris Barnett ◽  
Jocelyn E. Krebs

Williams syndrome transcription factor (WSTF) has emerged as an incredibly versatile nuclear protein. WSTF and the ATP-dependent chromatin remodeling complexes in which it exists, WINAC, WICH, and B-WICH, have been studied in a variety of organisms. This research has revealed roles for WSTF in a number of diverse molecular events. WSTF function includes chromatin assembly, RNA polymerase I and III gene regulation, vitamin D metabolism, and DNA repair. In addition to functioning as a subunit of several ATP-dependent chromatin remodeling complexes, WSTF binds specifically to acetylated histones and is itself a histone kinase as well as a target of phosphorylation. This review will describe the three known WSTF-containing complexes and discuss their various roles as well as mechanisms of regulating WSTF activity.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Sarah M. Innis ◽  
Birgit Cabot

Abstract ATP-dependent chromatin remodeling by histone-modifying enzymes and chromatin remodeling complexes is crucial for maintaining chromatin organization and facilitating gene transcription. In the SWI/SNF family of ATP-dependent chromatin remodelers, distinct complexes such as BAF, PBAF, GBAF, esBAF and npBAF/nBAF are of particular interest regarding their implications in cellular differentiation and development, as well as in various diseases. The recently identified BAF subcomplex GBAF is no exception to this, and information is emerging linking this complex and its components to crucial events in mammalian development. Furthermore, given the essential nature of many of its subunits in maintaining effective chromatin remodeling function, it comes as no surprise that aberrant expression of GBAF complex components is associated with disease development, including neurodevelopmental disorders and numerous malignancies. It becomes clear that building upon our knowledge of GBAF and BAF complex function will be essential for advancements in both mammalian reproductive applications and the development of more effective therapeutic interventions and strategies. Here, we review the roles of the SWI/SNF chromatin remodeling subcomplex GBAF and its subunits in mammalian development and disease.


2015 ◽  
Vol 48 (4) ◽  
pp. 465-470 ◽  
Author(s):  
Yahli Lorch ◽  
Roger D. Kornberg

AbstractThe nucleosome serves as a general gene repressor by the occlusion of regulatory and promoter DNA sequences. Repression is relieved by the SWI/SNF-RSC family of chromatin-remodeling complexes. Research reviewed here has revealed the essential features of the remodeling process.


2004 ◽  
Vol 82 (4) ◽  
pp. 482-489 ◽  
Author(s):  
Sara S Dirscherl ◽  
Jocelyn E Krebs

The yeast SWI/SNF ATP-dependent chromatin remodeling complex was first identified and characterized over 10 years ago (F. Winston and M. Carlson. 1992. Trends Genet. 8: 387–391.) Since then, the number of distinct ATP-dependent chromatin remodeling complexes and the variety of roles they play in nuclear processes have become dizzying (J.A. Martens and F. Winston. 2003. Curr. Opin. Genet. Dev. 13: 136–142; A. Vacquero et al. 2003. Sci. Aging Knowledge Environ. 2003: RE4) — and that does not even include the companion suite of histone modifying enzymes, which exhibit a comparable diversity in both number of complexes and variety of functions (M.J. Carrozza et al. 2003. Trends Genet. 19: 321–329; W. Fischle et al. 2003. Curr. Opin. Cell Biol. 15: 172–183; M. Iizuka and M.M. Smith. 2003. Curr. Opin. Genet. Dev. 13: 1529–1539). This vast complexity is hardly surprising, given that all nuclear processes that involve DNA — transcription, replication, repair, recombination, sister chromatid cohesion, etc. — must all occur in the context of chromatin. The SWI/SNF-related ATP-dependent remodelers are divided into a number of subfamilies, all related by the SWI2/SNF2 ATPase at their catalytic core. In nearly every species where researchers have looked for them, one or more members of each subfamily have been identified. Even the budding yeast, with its comparatively small genome, contains eight different chromatin remodelers in five different subfamilies. This review will focus on just one subfamily, the Imitation Switch (ISWI) family, which is proving to be one of the most diverse groups of chromatin remodelers in both form and function.


2021 ◽  
Author(s):  
Alejandro Saettone ◽  
Jyoti Garg ◽  
Jean-Philippe Lambert ◽  
Syed Nabeel-Shah ◽  
Marcelo Ponce ◽  
...  

Background The chromatin remodelers of the SWI/SNF family are critical transcriptional regulators. Recognition of lysine acetylation through a bromodomain (BRD) component is key to SWI/SNF function; in most eukaryotes, this function is attributed to SNF2/Brg1. Results Using affinity purification coupled to mass spectrometry (AP–MS) we identified members of a SWI/SNF complex (SWI/SNFTt) in Tetrahymena thermophila. SWI/SNFTt is composed of 11 proteins, Snf5Tt, Swi1Tt, Swi3Tt, Snf12Tt, Brg1Tt, two proteins with potential chromatin-interacting domains and four proteins without orthologs to SWI/SNF proteins in yeast or mammals. SWI/SNFTt subunits localize exclusively to the transcriptionally active macronucleus during growth and development, consistent with a role in transcription. While Tetrahymena Brg1 does not contain a BRD, our AP–MS results identified a BRD-containing SWI/SNFTt component, Ibd1 that associates with SWI/SNFTt during growth but not development. AP–MS analysis of epitope-tagged Ibd1 revealed it to be a subunit of several additional protein complexes, including putative SWRTt, and SAGATt complexes as well as a putative H3K4-specific histone methyl transferase complex. Recombinant Ibd1 recognizes acetyl-lysine marks on histones correlated with active transcription. Consistent with our AP–MS and histone array data suggesting a role in regulation of gene expression, ChIP-Seq analysis of Ibd1 indicated that it primarily binds near promoters and within gene bodies of highly expressed genes during growth. Conclusions Our results suggest that through recognizing specific histones marks, Ibd1 targets active chromatin regions of highly expressed genes in Tetrahymena where it subsequently might coordinate the recruitment of several chromatin-remodeling complexes to regulate the transcriptional landscape of vegetatively growing Tetrahymena cells.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Alisha Schlichter ◽  
Margaret M Kasten ◽  
Timothy J Parnell ◽  
Bradley R Cairns

SWI/SNF-family chromatin remodeling complexes, such as S. cerevisiae RSC, slide and eject nucleosomes to regulate transcription. Within nucleosomes, stiff DNA sequences confer spontaneous partial unwrapping, prompting whether and how SWI/SNF-family remodelers are specialized to remodel partially-unwrapped nucleosomes. RSC1 and RSC2 are orthologs of mammalian PBRM1 (polybromo) which define two separate RSC sub-complexes. Remarkably, in vitro the Rsc1-containing complex remodels partially-unwrapped nucleosomes much better than does the Rsc2-containing complex. Moreover, a rsc1Δ mutation, but not rsc2Δ, is lethal with histone mutations that confer partial unwrapping. Rsc1/2 isoforms both cooperate with the DNA-binding proteins Rsc3/30 and the HMG protein, Hmo1, to remodel partially-unwrapped nucleosomes, but show differential reliance on these factors. Notably, genetic impairment of these factors strongly reduces the expression of genes with wide nucleosome-deficient regions (e.g., ribosomal protein genes), known to harbor partially-unwrapped nucleosomes. Taken together, Rsc1/2 isoforms are specialized through composition and interactions to manage and remodel partially-unwrapped nucleosomes.


Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 3955-3966 ◽  
Author(s):  
O. Papoulas ◽  
S.J. Beek ◽  
S.L. Moseley ◽  
C.M. McCallum ◽  
M. Sarte ◽  
...  

The trithorax group gene brahma (brm) encodes an activator of Drosophila homeotic genes that functions as the ATPase subunit of a large protein complex. To determine if BRM physically interacts with other trithorax group proteins, we purified the BRM complex from Drosophila embryos and analyzed its subunit composition. The BRM complex contains at least seven major polypeptides. Surprisingly, the majority of the subunits of the BRM complex are not encoded by trithorax group genes. Furthermore, a screen for enhancers of a dominant-negative brm mutation identified only one trithorax group gene, moira (mor), that appears to be essential for brm function in vivo. Four of the subunits of the BRM complex are related to subunits of the yeast chromatin remodeling complexes SWI/SNF and RSC. The BRM complex is even more highly related to the human BRG1 and hBRM complexes, but lacks the subunit heterogeneity characteristic of these complexes. We present biochemical evidence for the existence of two additional complexes containing trithorax group proteins: a 2 MDa ASH1 complex and a 500 kDa ASH2 complex. These findings suggest that BRM plays a role in chromatin remodeling that is distinct from the function of most other trithorax group proteins.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
R Stefan Isaac ◽  
Fuguo Jiang ◽  
Jennifer A Doudna ◽  
Wendell A Lim ◽  
Geeta J Narlikar ◽  
...  

The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo.


2007 ◽  
Vol 85 (4) ◽  
pp. 419-425 ◽  
Author(s):  
Martin Montecino ◽  
Janet L. Stein ◽  
Gary S. Stein ◽  
Jane B. Lian ◽  
Andre J. van Wijnen ◽  
...  

Chromatin organization within the nuclear compartment is a fundamental mechanism to regulate the expression of eukaryotic genes. During the last decade, a number of nuclear protein complexes with the ability to remodel chromatin and regulate gene transcription have been reported. Among these complexes is the SWI/SNF family, which alters chromatin structure in an ATP-dependent manner. A considerable effort has been made to understand the molecular mechanisms by which SWI/SNF catalyzes nucleosome remodeling. However, limited attention has been dedicated to studying the role of the DNA sequence in this remodeling process. Therefore, in this minireview, we discuss the contribution of nucleosome positioning and nucleosome excluding sequences to the targeting and activity of SWI/SNF complexes. This discussion includes results from our group using the rat osteocalcin gene promoter as a model. Based on these results, we postulate a model for chromatin remodeling and transcriptional activation of this gene in osteoblastic cells.


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