Epigenetics and cancer

In the paper

“Epigenetic gene regulation collaborates with genetic alterations in cancer development.”

In the paper

“This is evident from every aspect of tumor biology including cell growth and differentiation, cell cycle control, DNA repair, angiogenesis, migration, and evasion of host immunosurveillance.”

In the paper

“However, other genes, such as cell cycle checkpoint genes and genes directly affected by exogenous stimuli such as growth factors or cell-cell contact, likely reside in a balanced state sensitive to dynamic adjustments in histone modifications, thereby allowing for rapid responses to specific stimuli.”

In the paper

“Ser 10 phosphorylation also facilitates acetylation of Lys 9, thereby preventing the setting of repressive Lys 9 methylation marks (Rea et al. 2000).”

What the sources say

• Not checked yetcites Rea et al. 2000

In the paper

“Not surprisingly therefore, epigenetic gene regulation is characterized overall by a high degree of integrity and stability.”

In the paper

“Trimethylation of Lys 4 on histone H3 correlates with transcriptional activity (Santos-Rosa et al. 2002),”

What the sources say

• Not checked yetcites Santos-Rosa et al. 2002

In the paper

“EZH2 is overexpressed in many cancers (Varambally et al. 2002;Bracken et al. 2003;Kleer et al. 2003;Raaphorst et al. 2003)”

What the sources say

• Not checked yetcites Varambally et al. 2002
• Not checked yetcites Bracken et al. 2003
• Not checked yetcites Kleer et al. 2003

In the paper

“the expression level of EZH2 correlates with a poorer prognosis in both prostate (Varambally et al. 2002) and breast cancer (Kleer et al. 2003).”

What the sources say

• Not checked yetcites Varambally et al. 2002
• Not checked yetcites Kleer et al. 2003

In the paper

“and the other four human MLL homologs all reside in cancer-related loci.”

In the paper

“A second group of proteins, containing bromodomain and chromodomain modules, use the epigenetic marks on the histone tails as recognition landmarks to bind the chromatin and initiate downstream biological processes such as chromatin compaction, transcriptional regulation, or DNA repair (Fig. 2).”

In the paper

“Together with the Trithorax group (TrxG) of proteins, which form positively acting transcriptional regulators (see following), the PcG complexes are thought to constitute a cellular memory system responsible for maintaining the epigenetic status of target genes throughout the lifetime of the organism (Jacobs and van Lohuizen 1999;Orlando 2003;Lund and van Lohuizen 2004).”

What the sources say

• Not checked yetcites Jacobs and van Lohuizen 1999
• Not checked yetcites Orlando 2003
• Not checked yetcites Lund and van Lohuizen 2004

In the paper

“With the exception of controlled genomic rearrangements, such as those of the immunoglobulin and T-cell receptor genes in B and T cells, all other differentiation processes are initiated or maintained through epigenetic processes.”

In the paper

“RNAi-mediated knockdown of EZH2 or EED in human primary or transformed cells results in a block of proliferation (Varambally et al. 2002;Bracken et al. 2003),”

What the sources say

• Not checked yetcites Varambally et al. 2002
• Not checked yetcites Bracken et al. 2003

In the paper

“In somatic cells, the transcriptional status of most genes is epigenetically fixed.”

In the paper

“and one study found MLL1 to reside in a large protein assembly containing subunits capable of regulating transcription preinitiation, nucleosome remodeling, histone acetylation, and histone methylation (Nakamura et al. 2002).”

What the sources say

• Not checked yetcites Nakamura et al. 2002

In the paper

“MLL1 has been found to associate with other epigenetic regulators, such as the HAT CBP (Ernst et al. 2001) and INI1 (Rozenblatt-Rosen et al. 1998), a subunit of the SWI/SNF nucleosome remodeling complex,”

What the sources say

• Not checked yetcites Ernst et al. 2001
• Not checked yetcites Rozenblatt-Rosen et al. 1998

In the paper

“Interestingly, emerging data suggest that the PRC2 complex composition may influence the type of methylation imprint imposed by EZH2, thereby adding yet another level of regulation (Kuzmichev et al. 2004).”

What the sources say

• Not checked yetcites Kuzmichev et al. 2004

In the paper

“The mixed lineage leukemia gene (MLL1, also known as HRX or ALL1) is involved in 11q23 translocations in acute leukemias (Djabali et al. 1992;Gu et al. 1992;Tkachuk et al. 1992),”

What the sources say

• Not checked yetcites Djabali et al. 1992
• Not checked yetcites Gu et al. 1992
• Not checked yetcites Tkachuk et al. 1992

In the paper

“Several SET (SuVar39, Enhancer of Zeste, and Trithorax) domain proteins have been demonstrated to be methyltransferases capable of covalently altering the lysine residues of histone proteins.”

In the paper

“Both PRC1 and PRC2 complex members have been linked to cell cycle control and cancer.”

In the paper

“Hence, some histone modifications may act as molecular switches, enabling or blocking the setting of other covalent marks (Fischle et al. 2003).”

What the sources say

• Not checked yetcites Fischle et al. 2003

In the paper

“In combination with other covalent modifications such as acetylation, phosphorylation, and ubiquitination, methylations of histone proteins are thought to represent an epigenetic code by the creation of binding interfaces for proteins involved in chromatin regulation (Strahl and Allis 2000;Jenuwein and Allis 2001;Lachner et al. 2003).”

What the sources say

• Not checked yetcites Strahl and Allis 2000
• Not checked yetcites Jenuwein and Allis 2001
• Not checked yetcites Lachner et al. 2003

In the paper

“and MLL1 was recently shown to be a histone H3 Lys 4-specific methyltransferase (Milne et al. 2002;Nakamura et al. 2002).”

What the sources say

• Not checked yetcites Milne et al. 2002
• Not checked yetcites Nakamura et al. 2002

In the paper

“Many SET domain proteins have been tightly linked to cancer development (Huang 2002;Schneider et al. 2002)”

What the sources say

• Not checked yetcites Huang 2002
• Not checked yetcites Schneider et al. 2002

In the paper

“Evidence is accumulating that suggests that the intrinsic stability is caused by multiple interlocking feedback mechanisms between functionally unrelated epigenetic layers, such as DNA methyltransferases (DNMTs) and histone modifying enzymes, resulting in the stable commitment of a locus to a particular activity state.”

In the paper

“Perturbation of epigenetic balances may lead to alterations in gene expression, ultimately resulting in cellular transformation and malignant outgrowth;”

In the paper

“and mice lacking Riz1 function only are prone to tumor formation (Steele-Perkins et al. 2001).”

What the sources say

• Not checked yetcites Steele-Perkins et al. 2001

In the paper

“The RIZ gene is situated on chromosome 1p36 in one of the most frequently deleted regions in human cancers (Buyse et al. 1996;Huang 2002),”

What the sources say

• Not checked yetcites Buyse et al. 1996
• Not checked yetcites Huang 2002

In the paper

“The RIZ gene produces two proteins, RIZ1 and RIZ2, because of the use of alternative promoters.”

In the paper

“The RIZ1 SET domain was recently shown to be a histone H3 Lys 9specific methyltransferase (Kim et al. 2003).”

What the sources say

• Not checked yetcites Kim et al. 2003

In the paper

“A similarly orchestrated epigenetic regulation was demonstrated for the Drosophila Trithorax-like protein Ash1, a histone methyltransferase (HMT) capable of methylating Lys 4 and Lys 9 of histone H3 and Lys 20 on histone H4 (Beisel et al. 2002).”

What the sources say

• Not checked yetcites Beisel et al. 2002

In the paper

“This ancient repressive system is self-sustaining in a cyclic manner, as HP1 associates directly with SUV39H1.”

In the paper

“EVI1 acts dominantly over its presumed antagonist MDS-EVI1 (Soderholm et al. 1997;Sitailo et al. 1999),”

What the sources say

• Not checked yetcites Soderholm et al. 1997
• Not checked yetcites Sitailo et al. 1999

In the paper

“SUV39H1 is involved in stabilizing heterochromatic regions of the genome via trimethylation of histone H3 Lys 9 (Rea et al. 2000;Peters et al. 2001).”

What the sources say

• Not checked yetcites Rea et al. 2000
• Not checked yetcites Peters et al. 2001

In the paper

“and high EVI1 expression correlates with poor prognosis in patients with acute myeloid leukemia (Barjesteh van Waalwijk van Doorn-Khosrovani et al. 2003).”

What the sources say

• Not checked yetcites Barjesteh van Waalwijk van Doorn-Khosrovani et al. 2003

In the paper

“This methyl imprint creates an anchor point for chromodomain proteins of the HP1 family (Bannister et al. 2001;Lachner et al. 2001).”

What the sources say

• Not checked yetcites Bannister et al. 2001
• Not checked yetcites Lachner et al. 2001

In the paper

“Interestingly, recent data from Drosophila studies indicate that TrxG proteins such as Trx and Ash1, rather than being general transcriptional coactivators, specifically function to prevent inappropriate silencing mediated by the PcG of transcriptional repressors (Klymenko and Muller 2004).”

What the sources say

• Not checked yetcites Klymenko and Muller 2004

In the paper

“The oncogenic capacity of several MLL fusion proteins has been verified in transgenic mice (Corral et al. 1996;Dobson et al. 1999).”

What the sources say

• Not checked yetcites Corral et al. 1996
• Not checked yetcites Dobson et al. 1999

In the paper

“In other MLL translocation products, the fusion partner moiety is likely capable of sequestering coactivators or nucleosome remodeling factors contributing to oncogenesis (discussed in So and Cleary 2004).”

What the sources say

• Not checked yetcites So and Cleary 2004

In the paper

“Recent data have demonstrated that dimerization of the MLL fusion partners may be an important virtue in some translocations (So et al. 2003).”

What the sources say

• Not checked yetcites So et al. 2003

In the paper

“Tumor-derived mutants of pRB have been identified that do not bind SUV39H proteins, signifying the importance of the association (Nielsen et al. 2001).”

What the sources say

• Not checked yetcites Nielsen et al. 2001

In the paper

“Conversely, siRNA-mediated knockdown of SMYD3 in cell lines derived from hepatomas and colorectal cancers was shown to have growth-inhibitory effects (Hamamoto et al. 2004).”

What the sources say

• Not checked yetcites Hamamoto et al. 2004

In the paper

“Intriguingly, the known MLL target genes HoxA7 and HoxA9 are both required for leukemia induction by an MLL fusion oncogene (Ayton and Cleary 2003).”

What the sources say

• Not checked yetcites Ayton and Cleary 2003

In the paper

“Recently, Suv39h1/2 was also shown to be important for regulating the length of mammalian telomeres (Garcia-Cao et al. 2004).”

What the sources say

• Not checked yetcites Garcia-Cao et al. 2004

In the paper

“Rather, the fusion proteins appear to exert dominant-negative functions over wild-type MLL (Arakawa et al. 1998;Ayton and Cleary 2001).”

What the sources say

• Not checked yetcites Arakawa et al. 1998
• Not checked yetcites Ayton and Cleary 2001

In the paper

“and RIZ has been found to be inactivated by mutations or DNA methylation in a wide variety of human tumors including breast cancer, liver cancer, colorectal cancer, lung cancer, lymphomas, and melanomas (Chadwick et al. 2000;Du et al. 2001;Poetsch et al. 2002;Sasaki et al. 2002;Oshimo et al. 2004).”

What the sources say

• Not checked yetcites Chadwick et al. 2000
• Not checked yetcites Du et al. 2001
• Not checked yetcites Poetsch et al. 2002

In the paper

“HDACs have, not unlike DNA methylation, dualistic and opposite functions in cancer development.”

In the paper

“PRMT4/ CARM1 positively regulates transcription of, among others, estrogen receptor-responsive genes via binding to the histone acetyl transferase CPB/p300 and methylation of Arg 17 of histone H3 (Xu et al. 2001;Daujat et al. 2002).”

What the sources say

• Not checked yetcites Xu et al. 2001
• Not checked yetcites Daujat et al. 2002

In the paper

“Importantly, HDAC activity is often crucial to prepare the histone template for methyltransferases by removing acetyl groups obstructing methylation.”

In the paper

“To this end, methylation of Arg 3 of histone H4 by PRMT1 has been found to facilitate H4 acetylation and enhance transcriptional activity (Wang et al. 2001a).”

What the sources say

• Not checked yetcites Wang et al. 2001a

In the paper

“An emerging central theme is that several SET domain proteins can be found in a cancer-promoting and a cancer-preventing isoform.”

In the paper

“CBP and p300 are found disrupted by translocations in leukemia with translocation partners including MLL, MOZ, and MORF (Borrow et al. 1996;Sobulo et al. 1997;Panagopoulos et al. 2001).”

What the sources say

• Not checked yetcites Borrow et al. 1996
• Not checked yetcites Sobulo et al. 1997
• Not checked yetcites Panagopoulos et al. 2001

In the paper

“This is true for the RIZ and MDS-EVI1 genes, both of which contain two promoters dictating separate protein isoforms, one form holding and one form lacking the SET domain.”

In the paper

“CBP and p300 are functional tumor suppressors as demonstrated by several lines of evidence.”

In the paper

“Finally, genetic ablation studies of Cbp and p300 in mouse models have confirmed that both proteins function as tumor suppressors (Yao et al. 1998;Kung et al. 2000;Kang-Decker et al. 2004).”

What the sources say

• Not checked yetcites Yao et al. 1998
• Not checked yetcites Kung et al. 2000
• Not checked yetcites Kang-Decker et al. 2004

In the paper

“Importantly, HDACs are associated with a number of other epigenetic repression mechanisms, including histone methylation (Ogawa et al. 2002;Vaute et al. 2002), PcG-mediated repression (van der Vlag and Otte 1999), and DNA methylation (Fuks et al. 2000;Rountree et al. 2000).”

What the sources say

• Not checked yetcites Ogawa et al. 2002
• Not checked yetcites Vaute et al. 2002
• Not checked yetcites van der Vlag and Otte 1999

In the paper

“Both HATs and HDACs have been found mutated or deregulated in various cancers.”

In the paper

“HDACs are, moreover, often found as”

In the paper

“On the one hand, HDACs play prominent roles in the transcriptional inactivation of tumor-suppressor genes.This is evident from studies using pharmacological inhibitors of HDAC activity in cancer therapies (discussed following).”

In the paper

“The two closely related HATs, p300 and CBP, act as transcriptional cofactors for a range of cellular oncoproteins, such as MYB, JUN, FOS, RUNX, BRCA1, p53, and pRB, as well as for the viral oncoproteins E1A, E6, and SV40 large T (for review, see Caron et al. 2003;Iyer et al. 2004).”

What the sources say

• Not checked yetcites Caron et al. 2003
• Not checked yetcites Iyer et al. 2004

In the paper

“Likewise, cell culture studies have demonstrated an important role for DNMT3A in cancer cell survival (Beaulieu et al. 2002).”

What the sources say

• Not checked yetcites Beaulieu et al. 2002

In the paper

“Together, these findings have led to the ying-yang theory (Huang 2002), proposing that the natural homeostasis existing between protein isoforms with and without SET domain is perturbated in cancers, resulting in selective expression of the oncogenic over the tumor-suppressive isoform.”

What the sources say

• Not checked yetcites Huang 2002

In the paper

“and DNMT1 knockdown experiments in human cancer cell lines have demonstrated an essential role for DNMT1 in maintaining aberrant repression of tumor-suppressor loci (Robert et al. 2003).”

What the sources say

• Not checked yetcites Robert et al. 2003

In the paper

“Interestingly, microarray analyses have re-vealed that the aberrant methylation patterns associated with cancer appears to be tumor-type specific”

What the sources say

• Not checked yetcites Eads et al. 2000
• Not checked yetcites Esteller et al. 2001

In the paper

“large-scale attempts to link epigenetic variation, such as methylation-variable positions, are currently being undertaken (Novik et al. 2002;Fazzari and Greally 2004”

What the sources say

• Not checked yetcites Novik et al. 2002
• Not checked yetcites Fazzari and Greally 2004

In the paper

“In normal cells, insulator proteins such as the transcription factor CTCF establish chromatin boundaries”

What the sources say

• Not checked yetcites Fedoriw et al. 2004
• Not checked yetcites Lewis and Murrell 2004

In the paper

“Indeed, links between hypomethylation and genomic instability have been shown for many cancer types including breast cancer (Tsuda et al. 2002) and prostate cancer (Schulz et al. 2002).”

What the sources say

• Not checked yetcites Tsuda et al. 2002
• Not checked yetcites Schulz et al. 2002

In the paper

“mice carrying a hypomorph Dnmt1 allele develop aggressive lymphomas displaying a high frequency of genomic rearrangements (Gaudet et al. 2003).”

What the sources say

• Not checked yetcites Gaudet et al. 2003

In the paper

“embryonic stem cells deficient for the Dnmt1 maintenance methyltransferase display an increased frequency of chromosomal rearrangements (Chen et al. 1998)”

What the sources say

• Not checked yetcites Chen et al. 1998

In the paper

“A decrease in global methylation can be detected prior to tumor formation in rats maintained on a methyldeficient diet (Christman et al. 1993;Pogribny et al. 1997),”

What the sources say

• Not checked yetcites Christman et al. 1993
• Not checked yetcites Pogribny et al. 1997

In the paper

“Loss of DNA methylation has also been linked to nutrition, as lack of S-adenosylmethione, the primary methyl donor in the cell, has been shown to predispose to cancer (Huang 2002).”

What the sources say

• Not checked yetcites Huang 2002

In the paper

“Ectopic cytosine hypermethylation is generally associated with transcriptional repression and, ultimately, tumor formation.”

In the paper

“methylation of the CTCF recognition sequence abolishes CTCF binding (Nakagawa et al. 2001)”

What the sources say

• Not checked yetcites Nakagawa et al. 2001

In the paper

“Spreading of heterochromatin-associated repression may be concurrent with the breakdown of higherorder chromatin structures such as boundary elements.”

In the paper

“indicating that specific DNA methylations may have long-range consequences.”

In the paper

“evidence from several model systems has demonstrated that histone methylation imprint may direct DNA methylation (Tamaru and Selker 2001;Bachman et al. 2003).”

What the sources say

• Not checked yetcites Tamaru and Selker 2001
• Not checked yetcites Bachman et al. 2003

In the paper

“Transcriptional silencing of genes with tumor-suppressive function may also occur via spreading of heterochromatin out from nearby silenced loci of repetitive DNA (Jones and Baylin 2002)”

What the sources say

• Not checked yetcites Jones and Baylin 2002

In the paper

“that the aberrant methylation patterns associated with cancer appears to be tumor-type specific (Eads et al. 2000;Esteller et al. 2001;Adorjan et al. 2002;Paz et al. 2003).”

What the sources say

• Not checked yetcites Eads et al. 2000
• Not checked yetcites Esteller et al. 2001
• Not checked yetcites Adorjan et al. 2002

In the paper

“and hypomethylation has been found to increase the expression of several known oncogenes including CYCLIN D2 (Oshimo et al. 2003), BCL2 (Hanada et al. 1993), and HRAS (Feinberg and Vogelstein 1983b).”

What the sources say

• Not checked yetcites Oshimo et al. 2003
• Not checked yetcites Hanada et al. 1993
• Not checked yetcites Feinberg and Vogelstein 1983b

In the paper

“acetylated lysines serve as binding sites for bromodomain-containing proteins, such as HATs and chromatin remodeling factors, some of which take part in the transcription initiation complex (Dhalluin et al. 1999;Zeng and Zhou 2002;Kanno et al. 2004).”

What the sources say

• Not checked yetcites Dhalluin et al. 1999
• Not checked yetcites Zeng and Zhou 2002
• Not checked yetcites Kanno et al. 2004

In the paper

“Studies of remethylation of the p16 INK4A tumor-suppressor gene following genome-wide demethylation indicates a requirement for DNA replication prior to remethylation (Velicescu et al. 2002).”

What the sources say

• Not checked yetcites Velicescu et al. 2002

In the paper

“On a more positive note, global demethylation results in the expression of”

What the sources say

• Not checked yetcites De Smet et al. 1996
• Not checked yetcites Banchereau et al. 2003

In the paper

“By extension, epigenetic silencing may underlie genetic cancer causes.”

In the paper

“Collaboration between genetic and epigenetic cancer causes has been directly demonstrated by examples in which one tumor-suppressor allele is inactivated by mutations and the other allele is transcriptionally silenced because of hypermethylation (Myohanen et al. 1998;Grady et al. 2000).”

What the sources say

• Not checked yetcites Myohanen et al. 1998
• Not checked yetcites Grady et al. 2000

In the paper

“and silencing of the DNA repair gene coding for O6methylguanine-DNA methyltransferase has been associated with specific mutations in K-RAS (Esteller et al. 2000) and p53 (Nakamura et al. 2001).”

What the sources say

• Not checked yetcites Esteller et al. 2000
• Not checked yetcites Nakamura et al. 2001

In the paper

“The methylation imprint set by EZH2 at Lys 27 on histone H3 mechanistically links the PRC2 and PRC1 PcG complexes, as methylated Lys 27 of histone H3 serves as a binding site for the PRC1 member Pc (Cao et al. 2002;Czermin et al. 2002;Kuzmichev et al. 2002).”

What the sources say

• Not checked yetcites Cao et al. 2002
• Not checked yetcites Czermin et al. 2002
• Not checked yetcites Kuzmichev et al. 2002

In the paper

“analyses of the SWI/SNF core subunit SNF5 (INI1) have revealed the presence of inactivating mutations in highly aggressive human malignant rhabdoid tumors (Versteege et al. 1998;Biegel et al. 1999).”

What the sources say

• Not checked yetcites Versteege et al. 1998
• Not checked yetcites Biegel et al. 1999

In the paper

“H2AX therefore appears to constitute a bona fide epigenetic tumor suppressor mechanism.”

In the paper

“the three mammalian HP1 members all hold chromodomains capable of recognizing the methylated Lys 9 on histone H3 (Bannister et al. 2001;Lachner et al. 2001)”

What the sources say

• Not checked yetcites Bannister et al. 2001
• Not checked yetcites Lachner et al. 2001

In the paper

“Such compensatory mecha-nisms were demonstrated recently in mouse ES cells deficient for both Suv39 homologs (Peters et al. 2003).”

What the sources say

• Not checked yetcites Peters et al. 2003

In the paper

“Bmi1 proved indispensable for the maintenance of hematopoietic and leukemic stem cells (Lessard and Sauvageau 2003;Park et al. 2003)”

What the sources say

• Not checked yetcites Lessard and Sauvageau 2003
• Not checked yetcites Park et al. 2003

In the paper

“Hence, ample evidence exists connecting PcG-mediated epigenetic repression to cancer development.”

In the paper

“perhaps surprisingly, no firm cancer connections have been established for any of the methylbinding proteins.”

In the paper

“mouse models demonstrating Snf5 as a haploinsufficient tumor-suppressor gene (Klochendler-Yeivin et al. 2000;Roberts et al. 2000)”

What the sources say

• Not checked yetcites Klochendler-Yeivin et al. 2000
• Not checked yetcites Roberts et al. 2000

In the paper

“Nucleosome remodeling complexes modify chromatin topology in an ATP-dependent manner by disrupting DNA:histone interactions, thereby facilitating sliding of the nucleosome, and hence the accessibility of the DNA to transcription factors (Becker and Horz 2002).”

What the sources say

• Not checked yetcites Becker and Horz 2002

In the paper

“methyl-DNA-binding proteins have been found associated with aberrantly methylated promoter regions of cancer-relevant genes such as p16CDKN2A (Nguyen et al. 2001) and MGMT (Nakagawachi et al. 2003).”

What the sources say

• Not checked yetcites Nguyen et al. 2001
• Not checked yetcites Nakagawachi et al. 2003

In the paper

“mutation analysis from human lung and colon cancers revealed few changes in MBD1 or MBD2, indicating a limited role for these proteins in cancer (Bader et al. 2003).”

What the sources say

• Not checked yetcites Bader et al. 2003

In the paper

“when bred onto a bona fide model for intestinal cancer, the Apc min mouse, loss of Mbd2 significantly delays tumorigenesis (Sansom et al. 2003).”

What the sources say

• Not checked yetcites Sansom et al. 2003

In the paper

“hence, functional inactivation of SWI/SNF impinges on a multitude of cellular growth control pathways (for a recent review, see Roberts and Orkin 2004).”

What the sources say

• Not checked yetcites Roberts and Orkin 2004

In the paper

“the differences in subnuclear localizations point to the presence of additional mechanisms for localizing and tethering HP1 proteins.”

In the paper

“Bmi1 is the most extensively studied PRC1 member, which has been found to be overexpressed in human tumors (Bea et al. 2001;Vonlanthen et al. 2001;Leung et al. 2004).”

What the sources say

• Not checked yetcites Bea et al. 2001
• Not checked yetcites Vonlanthen et al. 2001
• Not checked yetcites Leung et al. 2004

In the paper

“Bmi1 was subsequently demonstrated to exert oncogenic effects through down-regulation of the CDK inhibitors p16 ink4a and p19 Arf , thereby impinging on both the pRB and the p53 pathways (Jacobs et al. 1999a,b).”

What the sources say

• Not checked yetcites Jacobs et al. 1999a,b

In the paper

“In cell culture models, BMI1 regulates replicative senescence in human fibroblasts and mammary epithelial cells via repression of p16 and indirectly via induction of hTert (Dimri et al. 2002;Itahana et al. 2003).”

What the sources say

• Not checked yetcites Dimri et al. 2002
• Not checked yetcites Itahana et al. 2003

In the paper

“The significance of epigenetic mechanisms for gene regulation in cancer is now evident”

In the paper

“SWI/SNF interacts with many protein complexes central to cancer development, such as RB, p53, MYC, MLL, BRCA1, and ␤-catenin”

What the sources say

• Not checked yetcites Roberts and Orkin 2004

In the paper

“Although MeCP2, MBD2, and MBD4 have been found down-regulated in human cancers (Zhu et al. 2004b)”

What the sources say

• Not checked yetcites Zhu et al. 2004b

In the paper

“many”

In the paper

“MBD2 knockdown in human cancer cell lines was found to suppress tumorigenesis in a mouse xenograft model (Ivanov et al. 2003;Campbell et al. 2004).”

What the sources say

• Not checked yetcites Ivanov et al. 2003
• Not checked yetcites Campbell et al. 2004

In the paper

“and neuronal stem cell populations (Molofsky et al. 2003;Leung et al. 2004).”

What the sources say

• Not checked yetcites Molofsky et al. 2003
• Not checked yetcites Leung et al. 2004

In the paper

“The study of epigenetic imprints is still in its infancy”