scholarly journals WSTF does it all: a multifunctional protein in transcription, repair, and replicationThis paper is one of a selection of papers published in a Special Issue entitled 31st Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal’s usual peer review process.

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.

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.


Blood ◽  
2012 ◽  
Vol 120 (24) ◽  
pp. 4720-4732 ◽  
Author(s):  
Veneta Krasteva ◽  
Manuel Buscarlet ◽  
Abigail Diaz-Tellez ◽  
Marie-Anne Bernard ◽  
Gerald R. Crabtree ◽  
...  

Abstract ATP-dependent SWI/SNF-like BAF chromatin remodeling complexes are emerging as key regulators of embryonic and adult stem cell function. Particularly intriguing are the findings that specialized assemblies of BAF complexes are required for establishing and maintaining pluripotent and multipotent states in cells. However, little is known on the importance of these complexes in normal and leukemic hemopoiesis. Here we provide the first evidence that the actin-related protein BAF53a, a subunit of BAF complexes preferentially expressed in long-term repopulating stem cells, is essential for adult hemopoiesis. Conditional deletion of BAF53a resulted in multilineage BM failure, aplastic anemia, and rapid lethality. These severe hemopoietic defects originate from a proliferative impairment of BM HSCs and progenitors and decreased progenitor survival. Using hemopoietic chimeras, we show that the impaired function of BAF53a-deficient HSCs is cell-autonomous and independent of the BM microenvironment. Altogether, our studies highlight an unsuspected role for BAF chromatin remodeling complexes in the maintenance of HSC and progenitor cell properties.


2009 ◽  
Vol 87 (1) ◽  
pp. 35-50 ◽  
Author(s):  
Mohammed Altaf ◽  
Andréanne Auger ◽  
Marcela Covic ◽  
Jacques Côté

The organization of the eukaryotic genome into chromatin makes it inaccessible to the factors required for gene transcription and DNA replication, recombination, and repair. In addition to histone-modifying enzymes and ATP-dependent chromatin remodeling complexes, which play key roles in regulating many nuclear processes by altering the chromatin structure, cells have developed a mechanism of modulating chromatin structure by incorporating histone variants. These variants are incorporated into specific regions of the genome throughout the cell cycle. H2A.Z, which is an evolutionarily conserved H2A variant, performs several seemingly unrelated and even contrary functions. Another H2A variant, H2A.X, plays a very important role in the cellular response to DNA damage. This review summarizes the recent developments in our understanding of the role of H2A.Z and H2A.X in the regulation of chromatin structure and function, focusing on their functional links with chromatin modifying and remodeling complexes.


2009 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
Ling Zhang ◽  
Kristi Jones ◽  
Feng Gong

The assembly of DNA into chromatin in eukaryotic cells affects all DNA-related cellular activities, such as replication, transcription, recombination, and repair. Rearrangement of chromatin structure during nucleotide excision repair (NER) was discovered more than 2 decades ago. However, the molecular basis of chromatin dynamics during NER remains undefined. Pioneering studies in the field of gene transcription have shown that ATP-dependent chromatin-remodeling complexes and histone-modifying enzymes play a critical role in chromatin dynamics during transcription. Similarly, recent studies have demonstrated that the SWI/SNF chromatin-remodeling complex facilitates NER both in vitro and in vivo. Additionally, histone acetylation has also been linked to the NER of ultraviolet light damage. In this article, we will discuss the role of these identified chromatin-modifying activities in NER.


2010 ◽  
Vol 88 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Jennifer Huen ◽  
Yoshito Kakihara ◽  
Francisca Ugwu ◽  
Kevin L. Y. Cheung ◽  
Joaquin Ortega ◽  
...  

Rvb1 and Rvb2 are highly conserved, essential AAA+ helicases found in a wide range of eukaryotes. The versatility of these helicases and their central role in the biology of the cell is evident from their involvement in a wide array of critical cellular complexes. Rvb1 and Rvb2 are components of the chromatin-remodeling complexes INO80, Swr-C, and BAF. They are also members of the histone acetyltransferase Tip60 complex, and the recently identified R2TP complex present in Saccharomyces cerevisiae and Homo sapiens; a complex that is involved in small nucleolar ribonucleoprotein (snoRNP) assembly. Furthermore, in humans, Rvb1 and Rvb2 have been identified in the URI prefoldin-like complex. In Drosophila, the Polycomb Repressive complex 1 contains Rvb2, but not Rvb1, and the Brahma complex contains Rvb1 and not Rvb2. Both of these complexes are involved in the regulation of growth and development genes in Drosophila. Rvbs are therefore crucial factors in various cellular processes. Their importance in chromatin remodeling, transcription regulation, DNA damage repair, telomerase assembly, mitotic spindle formation, and snoRNP biogenesis is discussed in this review.


2010 ◽  
Vol 88 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Kevin L. Y. Cheung ◽  
Jennifer Huen ◽  
Walid A. Houry ◽  
Joaquin Ortega

The Rvb1 and Rvb2 proteins are 2 members of the AAA+ family, involved in roles as diverse as chromatin remodeling, transcription, small nucleolar RNA maturation, cellular transformation, signaling of apoptosis and mitosis. These proteins are capable of playing a role in such diverse cellular activities because they are components of different macromolecular assemblies. In the last few years, there has been a number of groups reporting on the structure of purified Rvbs. The reported results have been rather controversial, because there are significant differences observed among the published structures in spite of the high degree of homology among these proteins. Surprisingly, contradictions are observed not only between structures representing the Rvb proteins from different species, but also between protein structures from the same species. This review describes the available Rvb structures from different species and also makes a comparative analysis of them. Finally, we identify some aspects of these structural studies worth pursuing in additional investigations to ensure that the reported structures reflect physiologically relevant conformations of the Rvb1–Rvb2 complex.


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