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Ophelia Papoulas

Bio: Ophelia Papoulas is an academic researcher from University of California, Santa Cruz. The author has contributed to research in topics: Biology & Chromatin remodeling. The author has an hindex of 10, co-authored 10 publications receiving 1471 citations.

Papers
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Journal ArticleDOI
TL;DR: It is found that ISWI mutations affect both cell viability and gene expression during Drosophila development and cause striking alterations in the structure of the male X chromosome.

421 citations

Journal ArticleDOI
TL;DR: The trithorax group gene brahma (brm) encodes an activator of Drosophila homeotic genes that functions as the ATPase subunit of a large protein complex as discussed by the authors.
Abstract: 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.

300 citations

Journal ArticleDOI
01 Jan 1998-Genetics
TL;DR: It is found that the complete loss of brm function decreases cell viability and causes defects in the peripheral nervous system of the adult and site-directed mutagenesis was used to investigate the functions of conserved regions of the BRM protein.
Abstract: The Drosophila brahma (brm) gene encodes an activator of homeotic genes related to the yeast chromatin remodeling factor SWI2/SNF2. Here, we report the phenotype of null and dominant-negative brm mutations. Using mosaic analysis, we found that the complete loss of brm function decreases cell viability and causes defects in the peripheral nervous system of the adult. A dominant-negative brm mutation was generated by replacing a conserved lysine in the ATP-binding site of the BRM protein with an arginine. This mutation eliminates brm function in vivo but does not affect assembly of the 2-MD BRM complex. Expression of the dominant-negative BRM protein caused peripheral nervous system defects, homeotic transformations, and decreased viability. Consistent with these findings, the BRM protein is expressed at relatively high levels in nuclei throughout the developing organism. Site-directed mutagenesis was used to investigate the functions of conserved regions of the BRM protein. Domain II is essential for brm function and is required for the assembly or stability of the BRM complex. In spite of its conservation in numerous eukaryotic regulatory proteins, the deletion of the bromodomain of the BRM protein has no discernible phenotype.

194 citations

Journal ArticleDOI
TL;DR: Examination of the distribution of the BRM complex on larval salivary gland polytene chromosomes suggests that the chromatin remodeling activity of theBRM complex plays a general role in facilitating transcription by RNA polymerase II.
Abstract: Drosophila brahma (brm) encodes the ATPase subunit of a 2 MDa complex that is related to yeast SWI/SNF and other chromatin-remodeling complexes. BRM was identified as a transcriptional activator of Hox genes required for the specification of body segment identities. To clarify the role of the BRM complex in the transcription of other genes, we examined its distribution on larval salivary gland polytene chromosomes. The BRM complex is associated with nearly all transcriptionally active chromatin in a pattern that is generally non-overlapping with that of Polycomb, a repressor of Hox gene transcription. Reduction of BRM function dramatically reduces the association of RNA polymerase II with salivary gland chromosomes. A few genes, such as induced heat shock loci, are not associated with the BRM complex; transcription of these genes is not compromised by loss of BRM function. The distribution of the BRM complex thus correlates with a dependence on BRM for gene activity. These data suggest that the chromatin remodeling activity of the BRM complex plays a general role in facilitating transcription by RNA polymerase II.

181 citations

Journal ArticleDOI
TL;DR: The Drosophila kismet gene encodes several large nuclear proteins that are ubiquitously expressed along the anterior-posterior axis, providing further evidence that alterations in chromatin structure are required to maintain the spatially restricted patterns of homeotic gene transcription.
Abstract: The Drosophila kismet gene was identified in a screen for dominant suppressors of Polycomb, a repressor of homeotic genes. Here we show that kismet mutations suppress the Polycomb mutant phenotype by blocking the ectopic transcription of homeotic genes. Loss of zygotic kismet function causes homeotic transformations similar to those associated with loss-of-function mutations in the homeotic genes Sex combs reduced and Abdominal-B. kismet is also required for proper larval body segmentation. Loss of maternal kismet function causes segmentation defects similar to those caused by mutations in the pair-rule gene even-skipped. The kismet gene encodes several large nuclear proteins that are ubiquitously expressed along the anterior-posterior axis. The Kismet proteins contain a domain conserved in the trithorax group protein Brahma and related chromatin-remodeling factors, providing further evidence that alterations in chromatin structure are required to maintain the spatially restricted patterns of homeotic gene transcription.

140 citations


Cited by
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Journal ArticleDOI
TL;DR: Although the intracellular transduction of the Notch signal is remarkably simple, with no secondary messengers, this pathway functions in an enormous diversity of developmental processes and its dysfunction is implicated in many cancers.
Abstract: A small number of signalling pathways are used iteratively to regulate cell fates, cell proliferation and cell death in development. Notch is the receptor in one such pathway, and is unusual in that most of its ligands are also transmembrane proteins; therefore signalling is restricted to neighbouring cells. Although the intracellular transduction of the Notch signal is remarkably simple, with no secondary messengers, this pathway functions in an enormous diversity of developmental processes and its dysfunction is implicated in many cancers.

2,450 citations

Journal ArticleDOI
TL;DR: This work addresses many aspects of remodeler biology: their targeting, mechanism, regulation, shared and unique properties, and specialization for particular biological processes.
Abstract: The packaging of chromosomal DNA by nucleosomes condenses and organizes the genome, but occludes many regulatory DNA elements. However, this constraint also allows nucleosomes and other chromatin components to actively participate in the regulation of transcription, chromosome segregation, DNA replication, and DNA repair. To enable dynamic access to packaged DNA and to tailor nucleosome composition in chromosomal regions, cells have evolved a set of specialized chromatin remodeling complexes (remodelers). Remodelers use the energy of ATP hydrolysis to move, destabilize, eject, or restructure nucleosomes. Here, we address many aspects of remodeler biology: their targeting, mechanism, regulation, shared and unique properties, and specialization for particular biological processes. We also address roles for remodelers in development, cancer, and human syndromes.

2,093 citations

Journal ArticleDOI
TL;DR: This review focuses on the involvement of CBP/p300 in the complex biological processes that affect cell growth, transformation, and development.
Abstract: CREB binding protein (CBP) and p300 were both identified initially in protein interaction assays–the former through its association with the transcription factor CREB (Chrivia et al. 1993) and the latter through its interaction with the adenoviral-transforming protein E1A (Stein et al. 1990; Eckner et al. 1994). The recognition that these two proteins, one involved in transcription and the other in cell transformation, had highly conserved sequences suggested that they had the potential to participate in a variety of cellular functions (Fig. 1). Several excellent reviews (Janknecht and Hunter 1996; Shikama et al. 1997; Giles et al. 1998) have addressed the transcriptional coactivator functions of CBP/p300; this review focuses on the involvement of these proteins in the complex biological processes that affect cell growth, transformation, and development.

1,691 citations

Journal ArticleDOI
18 Oct 2002-Cell
TL;DR: This work purified an ESC-E(Z) complex from Drosophila embryos and found four major subunits: ESC, E(Z), NURF-55, and the PcG repressor, SU( Z)12, which methylates lysine-27 of histone H3.

1,534 citations

Journal ArticleDOI
22 Feb 2002-Cell
TL;DR: How the activities of two major classes of chromatin-modifying complexes, ATP-dependent remodeling complexes and HAT or HDAC complexes might be coordinated to create a DNA template that is accessible to the general transcription apparatus is discussed.

1,533 citations