Search results for "Chromatin Assembly and Disassembly"
showing 10 items of 36 documents
An essential switch in subunit composition of a chromatin remodeling complex during neural development.
2007
Summary Mammalian neural stem cells (NSCs) have the capacity to both self-renew and to generate all the neuronal and glial cell-types of the adult nervous system. Global chromatin changes accompany the transition from proliferating NSCs to committed neuronal lineages, but the mechanisms involved have been unclear. Using a proteomics approach, we show that a switch in subunit composition of neural, ATP-dependent SWI/SNF-like chromatin remodeling complexes accompanies this developmental transition. Proliferating neural stem and progenitor cells express complexes in which BAF45a, a Kruppel/PHD domain protein and the actin-related protein BAF53a are quantitatively associated with the SWI2/SNF2-…
Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells
2009
Epigenetic mechanisms that maintain neurogenesis throughout adult life remain poorly understood(1). Trithorax group (trxG) and Polycomb group (PcG) gene products are part of an evolutionarily conserved chromatin remodelling system that activate or silence gene expression, respectively(2). Although PcG member Bmi1 has been shown to be required for postnatal neural stem cell self-renewal(3,4), the role of trxG genes remains unknown. Here we show that the trxG member Mll1 (mixed-lineage leukaemia 1) is required for neurogenesis in the mouse postnatal brain. Mll1-deficient subventricular zone neural stem cells survive, proliferate and efficiently differentiate into glial lineages; however, neur…
Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells
2010
BACKGROUND AND PURPOSE Efavirenz (EFV) is widely used in the treatment of HIV-1 infection. Though highly efficient, there is growing concern about EFV-related side effects, the molecular basis of which remains elusive. EXPERIMENTAL APPROACH In vitro studies were performed to address the effect of clinically relevant concentrations of EFV (10, 25 and 50 mu M) on human hepatic cells. KEY RESULTS Cellular proliferation and viability were reduced in a concentration-dependent manner. Analyses of the cell cycle and several cell death parameters (chromatin condensation, phosphatidylserine exteriorization, mitochondrial proapoptotic protein translocation and caspase activation) revealed that EFV tr…
Transcription of genes in the biosynthetic pathway for fumonisin mycotoxins is epigenetically and differentially regulated in the fungal maize pathog…
2012
ABSTRACT When the fungal pathogen Gibberella moniliformis (anamorph, Fusarium verticillioides ) colonizes maize and maize-based products, it produces class B fumonisin (FB) mycotoxins, which are a significant threat to human and animal health. FB biosynthetic enzymes and accessory proteins are encoded by a set of clustered and cotranscribed genes collectively named FUM, whose molecular regulation is beginning to be unraveled by researchers. FB accumulation correlates with the amount of transcripts from the key FUM genes, FUM1 , FUM21 , and FUM8 . In fungi in general, gene expression is often partially controlled at the chromatin level in secondary metabolism; when this is the case, the deac…
Chromatin remodeling regulation by small molecules and metabolites.
2010
The eukaryotic genome is a highly organized nucleoprotein structure comprising of DNA, histones, non-histone proteins, and RNAs, referred to as chromatin. The chromatin exists as a dynamic entity, shuttling between the open and closed forms at specific nuclear regions and loci based on the requirement of the cell. This dynamicity is essential for the various DNA-templated phenomena like transcription, replication, and repair and is achieved through the activity of ATP-dependent chromatin remodeling complexes and covalent modifiers of chromatin. A growing body of data indicates that chromatin enzymatic activities are finely and specifically regulated by a variety of small molecules derived f…
Multiple roles for ISWI in transcription, chromosome organization and DNA replication.
2003
ISWI functions as the ATPase subunit of multiple chromatin-remodeling complexes. These complexes use the energy of ATP hydrolysis to slide nucleosomes and increase chromatin fluidity, thereby modulating the access of transcription factors and other regulatory proteins to DNA. Here we discuss recent progress toward understanding the biological functions of ISWI, with an emphasis on its roles in transcription, chromosome organization and DNA replication.
Epigenomic k-mer dictionaries: shedding light on how sequence composition influences in vivo nucleosome positioning
2014
Abstract Motivation: Information-theoretic and compositional analysis of biological sequences, in terms of k-mer dictionaries, has a well established role in genomic and proteomic studies. Much less so in epigenomics, although the role of k-mers in chromatin organization and nucleosome positioning is particularly relevant. Fundamental questions concerning the informational content and compositional structure of nucleosome favouring and disfavoring sequences with respect to their basic building blocks still remain open. Results: We present the first analysis on the role of k-mers in the composition of nucleosome enriched and depleted genomic regions (NER and NDR for short) that is: (i) exhau…
Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay
2013
Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions…
ISWI Regulates Higher-Order Chromatin Structure and Histone H1 Assembly In Vivo
2007
Imitation SWI (ISWI) and other ATP-dependent chromatin-remodeling factors play key roles in transcription and other processes by altering the structure and positioning of nucleosomes. Recent studies have also implicated ISWI in the regulation of higher-order chromatin structure, but its role in this process remains poorly understood. To clarify the role of ISWI in vivo, we examined defects in chromosome structure and gene expression resulting from the loss of Iswi function in Drosophila. Consistent with a broad role in transcriptional regulation, the expression of a large number of genes is altered in Iswi mutant larvae. The expression of a dominant-negative form of ISWI leads to dramatic a…
Expression inactivation of SMARCA4 by microRNAs in lung tumors
2014
SMARCA4 is the catalytic subunit of the SWI/SNF chromatin-remodeling complex, which alters the interactions between DNA and histones and modifies the availability of the DNA for transcription. The latest deep sequencing of tumor genomes has reinforced the important and ubiquitous tumor suppressor role of the SWI/SNF complex in cancer. However, although SWI/SNF complex plays a key role in gene expression, the regulation of this complex itself is poorly understood. Significantly, an understanding of the regulation of SMARCA4 expression has gained in importance due to recent proposals incorporating it in therapeutic strategies that use synthetic lethal interactions between SMARCA4-MAX and SMAR…