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Ducasse, Miryam; Brown, Mark A.

doi:10.1186/1476-4598-5-60

Cited by 145 publications

(47 citation statements)

References 152 publications

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“…It has been previously reported that the normally fluctuating expression of ICBP90 in cycling cells is perturbed in most cancer cell lines (5,18,21,42). Since there is increasing evidence suggesting a role for epigenetic mechanisms in carcinogenesis (12,62), it would be interesting to determine if the role of ICBP90 in cancer is dependent upon its methyl K9 H3 binding activity. Our results outline several similarities of ICBP90 and Np95 and HP1, particularly the alpha and beta isoforms, such as recognition of methyl K9 H3, heterochromatic localization, and involvement in the establishment and/or maintenance of a higher-order chromatin organization.…”

Section: Discussionmentioning

confidence: 99%

ICBP90, a Novel Methyl K9 H3 Binding Protein Linking Protein Ubiquitination with Heterochromatin Formation

Karagianni

Amazit

Qin

et al. 2008

Molecular and Cellular Biology

217

240

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Methylation of histone H3 on lysine 9 is critical for diverse biological processes including transcriptional repression, heterochromatin formation, and X inactivation. The biological effects of histone methylation are thought to be mediated by effector proteins that recognize and bind to specific patterns of methylation. Using an unbiased in vitro biochemical approach, we have identified ICBP90, a transcription and cell cycle regulator, as a novel methyl K9 H3-specific binding protein. ICBP90 and its murine homologue Np95 are enriched in pericentric heterochromatin of interphase nuclei, and this localization is dependent on H3K9 methylation. Specific binding of ICBP90 to methyl K9 H3 depends on two functional domains, a PHD (plant homeodomain) finger that defines the binding specificity and an SRA (SET-and RING-associated) domain that promotes binding activity. Furthermore, we present evidence that ICBP90 is required for proper heterochromatin formation in mammalian cells.Covalent modifications of the histone tails regulate virtually all aspects of chromatin biology. In addition to affecting histone-histone and histone-DNA interactions, posttranslational marks on the histone tails exert their modulatory role by generating docking sites for downstream effectors. Such molecules, often possessing enzymatic activities, serve as readers of histone modifications and participate in vital cellular processes, including transcription, replication, chromosome segregation, recombination, and DNA repair (15,30,58).One of the most extensively studied histone tail modifications is methylation of histone H3 on lysine 9 (2). Histone H3 K9 methylation has been shown to be critical for regulation of gene expression, and it is enriched in transcriptionally inactive regions of the genome. It is considered a molecular mark of heterochromatin, the cytologically defined, gene-poor, and highly compacted regions of the chromatin. Interplay between H3 K9 methylation and DNA methylation has also been proposed in various models of heterochromatin formation and maintenance (32,43,51,65). Furthermore, H3 K9 methylation is implicated in gene silencing phenomena such as X chromosome inactivation in female mammals and DNA elimination in the microscopic protozoon Tetrahymena (4, 60).Several mammalian proteins, including SUV39H1, SUV39H2, G9a, ESET/SETDB1, and EuHTMase1, have been shown to have methyltransferase activity toward K9 of H3 (46,47,54,56,59,72). Though they target the same histone residue, important differences exist among the above enzymes regarding their chemistry and distribution and consequently their biological roles. The reversibility of H3 K9 methylation has been an object of speculation for many years. Evidence for the removal of this covalent mark was obtained recently with the identification of specific histone demethylases (10,17,34,40,66,67,71). Although reversible, methylation appears to be much more stable compared to other histone modifications. Therefore, it is considered to play a major role in the establishment and ma...

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Section: Discussionmentioning

confidence: 99%

ICBP90, a Novel Methyl K9 H3 Binding Protein Linking Protein Ubiquitination with Heterochromatin Formation

Karagianni

Amazit

Qin

et al. 2008

Molecular and Cellular Biology

217

240

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“…Cancer is a multistep process derived from combinational crosstalk between genetic alterations and epigenetic influences through various environmental factors [5,6,7]. In the nutritional field, epigenetics is exceptionally important, because nutrients and bioactive food components can modify epigenetic phenomena and alter the expression of genes at the transcriptional level [2,8,9].…”

Section: Epigenetic Overview Of Crcmentioning

confidence: 99%

“…Increasing evidence suggests that bioactive dietary components impact epigenetic processes often involved in the reactivation of tumor suppressor genes, the activation of cell survival proteins and the induction of cellular apoptosis in many types of cancer [11]. In addition to the transcriptional silencing of tumor suppressor genes and protein expression, noncoding miRNAs also regulate the expression of a myriad of cellular proteins by affecting mRNA stability and translation by epigenetic processes in cancer progression [5,6]. Interestingly, miRNAs can control the expression of various epigenetic modifying enzymes, such as DNA methyltransferases, histone methyltransferases, and HDACs, involved in carcinogenic processes [12,13].…”

Section: Epigenetic Overview Of Crcmentioning

confidence: 99%

Epigenetics, Probiotic Metabolites and Colon Cancer Prevention: An Overview of Progress, Opportunities and Challenges

Kumar¹,

Hemalatha²,

Kumar³

et al. 2013

Med Epigenet

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Colorectal cancer (CRC) is a common epithelial neoplasia across the globe, with about 1.2 million newly diagnosed cases and over 600,000 mortalities annually. The underlying causes are numerous including dietary ingredients, environmental factors and gut metabolome that affect colon cellular gene regulation and post-translational modifications of the proteome. Collectively, these alterations initiate epigenetic modifications leading to the inception of various metabolic diseases and malignancies. Epigenetics is at the core of modern medicine since it deals with complex processes that turn the expression of certain genes on and off, and it elucidates the mechanisms and connections between genotypes and the environment during various stages of life. However, the majority of the vertical molecular mechanisms with reference to epigenomics, epigenetic and metabolic ailments are still unidentified and need further research. This article summarizes the burgeoning role of probiotic metabolites and some prominent therapeutic dietary ingredients in the management of CRC.

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“…DNA that is normally methylated becomes unmethylated, while DNA that is supposed to be methylation free obtains the modification (Herman et al 1996;Baylin 2005;Feinberg et al 2006). This apparent redistribution of normal methylation patterning is regionally complex and is thought to be among the earliest molecular alterations during tumorigenesis (Lund and van Lohuizen 2004;Baylin 2005;Laird 2005;Ducasse and Brown 2006;Feinberg et al 2006); therefore, abnormal methylation marks may be useful as biomarkers for the early detection and diagnosis of different types of cancer (Paluszczak and Baer-Dubowska 2006 Serum is a very attractive medium for the development of cancer detection assays as is obtained through a simple, relatively noninvasive procedure. Several reports have documented the detection of DNA with cancer-associated changes (mutations, methylation, rearrangements) in the serum of patients; however, its precise origin is unclear.…”

mentioning

confidence: 99%

Massively parallel bisulphite pyrosequencing reveals the molecular complexity of breast cancer-associated cytosine-methylation patterns obtained from tissue and serum DNA

Korshunova¹,

Maloney²,

Lakey³

et al. 2007

Genome Res.

117

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Cytosine-methylation changes are stable and thought to be among the earliest events in tumorigenesis. Theoretically, DNA carrying tumor-specifying methylation patterns escape the tumors and may be found circulating in the sera from cancer patients, thus providing the basis for development of noninvasive clinical tests for early cancer detection. Indeed, using methylation-specific PCR-based techniques, several groups reported the detection of tumor-associated methylated DNA in the sera from cancer patients with varying clinical success. However, by design, such analytical approaches allow assessment of the presence of molecules with only one methylation pattern, leaving the bigger picture unexplored. The limited knowledge about circulating DNA methylation patterns hinders the efficient development of clinical methylation tests and testing platforms. Here, we report the results of a comprehensive methylation pattern analysis from breast cancer clinical tissues and sera obtained using massively parallel bisulphite pyrosequencing. The four loci studied were recently discovered by our group, and demonstrated to be powerful epigenetic biomarkers of breast cancer. The detailed analysis of more than 700,000 DNA fragments derived from more than 50 individuals (cancer and cancer-free) revealed an unappreciated complexity of genomic cytosine-methylation patterns in both tissue derived and circulating DNAs. Both tumor and cancer-free tissues (as well as sera) contained molecules with nearly every conceivable cytosine-methylation pattern at each locus. Tumor samples displayed more variation in methylation level than normal samples. Importantly, by establishing the methylation landscape within circulating DNA, this study has better defined the development challenges facing DNA methylation-based cancer-detection tests.

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Abstract: The correlation between epigenetic aberrations and disease underscores the importance of epigenetic mechanisms. Here, we review recent findings regarding chromatin modifications and their relevance to cancer.

Cited by 145 publications

References 152 publications

ICBP90, a Novel Methyl K9 H3 Binding Protein Linking Protein Ubiquitination with Heterochromatin Formation

ICBP90, a Novel Methyl K9 H3 Binding Protein Linking Protein Ubiquitination with Heterochromatin Formation

Epigenetics, Probiotic Metabolites and Colon Cancer Prevention: An Overview of Progress, Opportunities and Challenges

Massively parallel bisulphite pyrosequencing reveals the molecular complexity of breast cancer-associated cytosine-methylation patterns obtained from tissue and serum DNA

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