Chromatin dynamics and cancer

Guasconi, Valentina; Ait‐Si‐Ali, Slimane

doi:10.4161/cbt.3.9.1102

Cited by 9 publications

(5 citation statements)

References 33 publications

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“…Expression of the multiple isoforms of Sp3 is controlled by alternative translation initiations, with each isoforms having a unique role leading to either activation or repression of the MOR gene. There is increasing evidence that chromatin-remodeling factors are involved in several biological events, including cancer development (Guasconi and Ait-Si-Ali, 2004;Dey, 2006;Medina et al, 2008), ovarian germ and somatic cell development and differentiation (Pé pin et al, 2007), neuronal differentiation (Seo et al, 2005;Lessard et al, 2007), DNA damage repair (Pena and Pereira-Smith, 2007), embryonic stem cell neuronal differentiation (Meshorer, 2007), aging (Anastasiou and Krek, 2006), and immune cell development (Winandy, 2005). These findings indicate that chromatin remodeling plays an important role in gene regulation.…”

Section: Discussionmentioning

confidence: 93%

Up-Regulation of the μ-Opioid Receptor Gene Is Mediated through Chromatin Remodeling and Transcriptional Factors in Differentiated Neuronal Cells

Hwang¹,

Kim²,

Kim³

et al. 2010

Molecular Pharmacology

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The effects of morphine are mediated mainly through the opioid receptor (MOR). Expression of the MOR is upregulated during neuronal differentiation in P19 embryonal carcinoma cells and epigenetic changes play an important role in MOR up-regulation. This study investigates the basis for differentiation-dependent alterations of MOR chromatin by studying the recruitment or dissociation of several factors to the remodeled chromatin locus. Chromatin immunoprecipitation assays were used to demonstrate the recruitment of the transcriptional activator Sp1 and the chromatin remodeling factors Brg1 and BAF155 to this promoter, as well as the dissociation of repressors [histone deacetylases, mSin3A, Brm, and methyl-CpG-binding protein 2 (MeCP2)]. Histone modifications (acetylation, induction of histone H3-lys4 methylation, and reduction of H3-lys9 methylation) were consistently detected on this promoter. Overexpression of Sp1 strongly enhanced MOR promoter activity, and the histone deacetylase inhibitor trichostatin A also increased promoter activity. In vitro DNA CpG-methylation of the promoter partially blocked binding of the Sp1 factor but induced MeCP2 binding. Coimmunoprecipitation studies also found novel evidence of an endogenous MeCP2 interaction with Sp3 but a weaker interaction with Sp1. Overall, the results suggest that during neuronal differentiation, MeCP2 and DNA methylation mediate remodeling of the MOR promoter by chromatin remodeling factors (Brg1 and BAF155) from a compacted state to a conformation allowing access for transcriptional factors. Subsequent recruitment of the activating transcription factor Sp1 to the remodeled promoter results in MOR up-regulation.Opioid drugs, including endogenous opioid peptides and the analgesic drug morphine, exert their pharmacological and physiological effects through binding to opioid receptors. The three major types of opioid receptors (, ␦, and ) all belong to the G protein-coupled receptor superfamily. On agonist binding, these receptors couple to G proteins and affect several signal transduction pathways, including inhibition of adenylyl cyclases and Ca 2ϩ channels, activation of inward-rectifying K ϩ channels, transient increases of intracellular Ca 2ϩ levels, and activation of phospholipase C and the mitogen-activated protein kinases extracellular signalregulated kinases 1 and 2 (Law et al., 2000).The opioid receptor (MOR) is expressed mainly in the central nervous system with densities varying greatly in different brain regions displaying different functional roles (Mansour et al., 1995). The MOR-expressing brain regions are involved in motivating and rewarding behaviors mediated by opiates and other drugs of abuse. Furthermore, response to morphine varies in different neuronal cells and brain regions depending on receptor levels. Several studies suggest that the MOR plays a key role in mediating the major

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Section: Discussionmentioning

confidence: 93%

Up-Regulation of the μ-Opioid Receptor Gene Is Mediated through Chromatin Remodeling and Transcriptional Factors in Differentiated Neuronal Cells

Hwang¹,

Kim²,

Kim³

et al. 2010

Molecular Pharmacology

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“…Defects in chromatin-remodeling activity have been linked to severe diseases such as leukemia and epithelial cancers [52]. Two classes of chromatin remodelers function in DSB repair:INO80 and RSC [53,54].…”

Section: Genes Controlling Dna Mobility After Dna Damagementioning

confidence: 99%

DNA in motion during double-strand break repair

Miné-Hattab

Rothstein

2013

Trends in Cell Biology

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DNA organization and dynamics profoundly affect many biological processes such as gene regulation and DNA repair. In this review, we present the latest studies on DNA mobility in the context of DNA damage. Recent studies demonstrate that DNA mobility is dramatically increased in the presence of double-strand breaks (DSBs) in the yeast Saccharomyces cerevisiae. As a consequence, chromosomes explore a larger nuclear volume, facilitating homologous pairing but also increasing the rate of ectopic recombination. Increased DNA dynamics is dependent on several homologous recombination (HR) proteins and we are just beginning to understand how chromosome dynamics is regulated after DNA damage.

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“…The alteration of chromatin structure by histone acetyltransferases and histone deacetylases has been largely connected with carcinogenesis. Intriguingly, the selective inhibition of chromatin remodeling pathways has provided a new therapeutic window in cancer biology (5).…”

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confidence: 99%

Metastasis Tumor Antigen Family Proteins during Breast Cancer Progression and Metastasis in a Reliable Mouse Model for Human Breast Cancer

Zhang

Stephens

Kumar

2006

Clinical Cancer Research

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Purpose: Chromatin remodeling pathways are critical in the regulation of cancer-related genes and are currently being explored as potential targets for therapeutic intervention. The metastasis tumor antigen (MTA) family of proteins, MTA1, MTA2, and MTA3, are components of chromatin remodeling pathways with potential roles in breast cancer. Although all three MTA family proteins have been shown to be associated with metastatic progression of breast cancers, the expression characteristic of MTA1-3 proteins in a multistep breast cancer progression model remains unknown. Structural and functional studies have suggested that they are heterogeneous in the Mi-2/NuRD complex, exhibit tissue-specific patterns of expression, and impart unique properties to estrogen receptor-a (ERa) action. This led us to hypothesize that each member of the MTA family possesses a unique role and interacts with different pathways in the stepwise process of breast cancer development and progression. Experimental Design: MTA family proteins were examined by immunohistochemistry in breast cancer processes ranging from normal duct, to premalignant lesions, to invasive carcinoma, and to metastasized tumors in PyV-mT transgenic mice, which represents a reliable model for multistage tumorigenesis of human breast cancer. We also determined the association of MTA proteins with the status of cell proliferation, ER, E-cadherin and cytoplasmic h-catenin, and cancer-related coactivators, AIB1and PELP1. Results: The expression of all three MTA proteins was altered in primary breast tumors. Each MTA protein had a unique expression pattern during the primary breast tumor progression. Altered expression of MTA1was observed in both premalignant lesion and malignant carcinoma, but an elevated nuclear expression was observed in ER-negative carcinomas. MTA3 was exclusively expressed in a subset of cells of ER-positive premalignant lesions but not in carcinomas. MTA2 expression seems to be unrelated to ER status. Loss of MTA3 expression and more nuclear localization of MTA1 occurred with loss of E-cadherin and decreased cytoplasmic h-catenin, two molecules essential for epithelial cell adhesion and important tumor cell invasion. At the late stage of tumor formation, MTA1is usually expressed in the center of tumors. Coincidentally, the distribution of MTA1-positive cells at this stage was complementary to that of AIB1and PELP1, which were localized to the tumor periphery with relatively active cell proliferation, scattered ER-positive cells and a limited differentiation. In metastasized lung tumors, the expression pattern of MTAprotein expression was distinct from that in primary counterparts. Conclusions: The findings presented here support the notion that each member of the MTA family might potentially play a stepwise role in a cell type^specific manner during breast cancer progression to metastasis. On the basis of the noted temporal expression patterns of MTA proteins with ER status, cell adhesion^essential regulators (E-cadherin and cytoplasmic h-ca...

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Chromatin dynamics and cancer

Cited by 9 publications

References 33 publications

Up-Regulation of the μ-Opioid Receptor Gene Is Mediated through Chromatin Remodeling and Transcriptional Factors in Differentiated Neuronal Cells

Up-Regulation of the μ-Opioid Receptor Gene Is Mediated through Chromatin Remodeling and Transcriptional Factors in Differentiated Neuronal Cells

DNA in motion during double-strand break repair

Metastasis Tumor Antigen Family Proteins during Breast Cancer Progression and Metastasis in a Reliable Mouse Model for Human Breast Cancer

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