Chromatin modifier enzymes, the histone code and cancer

Santos‐Rosa, Helena; Caldas, Carlos

doi:10.1016/j.ejca.2005.08.010

Cited by 289 publications

(222 citation statements)

References 247 publications

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“…1 Furthermore, epigenetic analyses are of interest since epigenetic therapy is emerging as a valuable and effective treatment approach for peripheral T-cell lymphomas and is also envisaged for Bcell and Hodgkin's lymphomas. [2][3][4][5] There are different sets of epigenetic instructions involved in the regulation of gene expression.…”

Section: Introductionmentioning

confidence: 99%

Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation

Seitz¹,

Thomas²,

Zimmermann³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundEpigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin's lymphoma. However, little is known regarding epigenetic similarities between cells of classical Hodgkin's lymphoma and plasma cell myeloma, both of which share extinction of the gene expression program of mature B cells. Design and MethodsGlobal histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin's lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA polymerase chain reaction for selected genes. Epigenetic modifications were compared to gene expression data. ResultsCharacteristic B-cell genes were hypoacetylated in classical Hodgkin's lymphoma and plasma cell myeloma cell lines as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin' lymphoma and plasma cell myeloma cell lines, such as IRF4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected characteristic B-cell genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin's lymphoma than in plasma cell myeloma. ConclusionsOur epigenetic data support the view that classical Hodgkin's lymphoma is characterized by abortive plasma cell differentiation with a down-regulation of characteristic B-cell genes but without activation of most genes typical of plasma cells.

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Section: Introductionmentioning

confidence: 99%

Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation

Seitz¹,

Thomas²,

Zimmermann³

et al. 2011

Haematologica

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“…Alternatively, it might be an intrinsic characteristic of the yeast-display scFv library to generate scFv with preferential affinity for conformational epitopes (Weaver-Feldhaus et al, 2005). In either case, the ability of an affinity reagent to distinguish subtle conformational changes is a desirable characteristic for the accurate detection of biomarkers that often result from structural modifications of normal proteins through cleavage, aberrant transcriptions or post-translational modifications (Mahlknecht and Hoelzer, 2000;Brinkman, 2004;Venables, 2004;Kalnina et al, 2005;Santos-Rosa and Caldas, 2005).…”

Section: Discussionmentioning

confidence: 99%

Method for generation of in vivo biotinylated recombinant antibodies by yeast mating

Scholler

Garvik

Quarles

et al. 2006

Journal of Immunological Methods

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We describe here a novel method for generation of yeast-secreted, in vivo biotinylated recombinant antibodies, or biobodies. Biobodies are secreted by diploid yeast resulting from the fusion of two haploid yeast of opposite mating type. One yeast carries a cDNA encoding an antibody recognition sequence fused to an IgA1 hinge and a biotin acceptor site (BCCP) at the C-terminus; the other carries a cDNA encoding an E. Coli biotin ligase (BirA) fused to KEX2 golgi-localization sequences, so that BirA can catalyze the biotin transfer to the recognition sequence-fused BCCP within the yeast secretory compartment. We illustrate this technology with biobodies against HE4, a biomarker for ovarian carcinoma. Anti-HE4 biobodies were derived from clones or pools of anti-HE4-specific yeast-display scFv, constituting respectively monoclonal (mBb) or polyclonal (pBb) biobodies. Anti-HE4 biobodies were secreted directly biotinylated thus bound to labeled-streptavidin and streptavidin-coated surfaces without Ni-purification. Anti-HE4 biobodies demonstrated specificity and sensitivity by ELISA assays, flow cytometry analysis and western blots prior to any maturation; dissociation equilibrium constants as measured by surface plasmon resonance sensor were of K d = 4.8×10 -9 M and K d =5.1×10 -9 M before and after Ni-purification respectively. Thus, yeast mating permits cost-effective generation of biotinylated recombinant antibodies of high affinity.

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“…Both epigenetic processes appear to act jointly to regulate gene expression and the densely methylated DNA associated with transcriptionally inactive chromatin usually contains hypoacetylated histones. [40][41][42] Preclinical studies have shown that DNA methylation and histone deacetylation promote tumorigenesis and cancer progression in some entities and that their inhibition strongly suppresses cancer growth. 43 Hypomethylating agents, such as 5-azadeoxycytidine, are specific inhibitors of the DNA methyltransferase resulting in promoter hypomethylation and concomitant reexpression of tumor suppressor genes and miRNAs.…”

Section: Micrornas As Epigenetic Targetsmentioning

confidence: 99%

Epigenetic markers for chemosensitivity and chemoresistance in pancreatic cancer—A review

Dhayat

Mardin

Mees

et al. 2011

Intl Journal of Cancer

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Adjuvant first-line gemcitabine monochemotherapy presents a standard treatment for patients with advanced pancreatic adenocarcinoma and improves overall survival in chemosensitive patients. Nonetheless, 6-month progression-free survival remains below 15%, despite interdisciplinary approaches. The success of gemcitabine treatment is disappointing and-in the absence of reliable tumor markers-challenging to quantify. Epigenetic alterations have been recently identified to take on important roles in cancer development and possibly cancer treatment. In this context, microRNAs are becoming increasingly acknowledged as useful biomarkers for classifying cancers and providing information on their chemo-and radiosensitivity. This review illustrates the potential of genetic and epigenetic markers in the prediction of chemosensitivity in pancreatic cancer patients and in the monitoring of their response rates to adjuvant therapy.

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Chromatin modifier enzymes, the histone code and cancer

Cited by 289 publications

References 247 publications

Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation

Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation

Method for generation of in vivo biotinylated recombinant antibodies by yeast mating

Epigenetic markers for chemosensitivity and chemoresistance in pancreatic cancer—A review

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