The Dermatomyositis-Specific Autoantigen Mi2 Is a Component of a Complex Containing Histone Deacetylase and Nucleosome Remodeling Activities

Zhang, Yi; LeRoy, Gary; Seelig, H. P.; Lane, William S.; Reinberg, Danny

doi:10.1016/s0092-8674(00)81758-4

Cited by 746 publications

(677 citation statements)

References 59 publications

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“…For example, overexpression of Cyclin D1 has been shown to distinguish breast carcinomas and in situ breast lesions from benign lesions (WeinstatSaslow et al, 1995). Amongst other cDNAs up-regulated in the malignant cell library, were those corresponding to mRNAs for a putative G-protein-coupled receptor (Libert et al, 1989), for proteins associated with the mitotic spindle checkpoint, BUB3 (Brady and Hardwick, 2000) and with chromatin remodelling (Wang et al, 1996;Zhang et al, 1998;Vignali et al, 2000). Two cDNAs (LIM kinase and BUB3), which are differentially-expressed in the present malignant library, have also been found to be differentially expressed in a subtracted library representing cDNAs expressed in a pathologically homogeneous breast carcinoma specimen subtracted with cDNA from 50 000 ductal-carcinoma-in-situ cells microdissected from the surrounding normal tissue (Liu, 2001).…”

Section: Discussionmentioning

confidence: 99%

Identification of mRNAs differentially-expressed between benign and malignant breast tumour cells

et al. 2002

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Two suppression subtracted cDNA libraries have been constructed, one containing cDNAs to mRNAs present at a higher level in a benign human breast tumour-derived cell line relative to the malignant mammary cell line, MCF-7, and the other containing cDNAs present at a higher level in the MCF-7 cells relative to the benign cells. Randomly-picked cloned DNAs have been sequenced yielding 29 and 128 different cDNAs from the benign and malignant libraries, respectively. Using reverse Northern hybridisation, 76% and 83% of the cDNAs were differentially expressed by greater than two-fold, whilst 14% and 11% of cDNAs in the respective libraries were differentially expressed by more than 15-fold. Amongst these were oestrogenresponsive cDNAs and expressed sequence tags. One such oestrogen-responsive expressed sequence tag, M41, is transcribed from a gene located on chromosome 21q22.3, within an intron of a larger gene. The M41 gene contains oestrogen response elements, one of which is associated with alu repeats. M41 mRNA is expressed at a statistically significantly higher level in human breast cancer specimens than in normal human breast and benign lesions. In carcinomas, its up-regulation is associated with the development of the malignant cell.

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Section: Discussionmentioning

confidence: 99%

Identification of mRNAs differentially-expressed between benign and malignant breast tumour cells

et al. 2002

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“…The nucleosome remodeling and deacetylation (NuRD) complex contains at least seven polypeptides, including the ATPase Mi-2, the histone deacetylases HDAC1&2, Mta1&2 (Metastasis-associated protein1&2), and the methyl-binding domain proteins Mbd2&3. NuRD represses transcription by binding to methylated DNA, mediating heterochromatin formation, and transcriptional silencing [12,13]. Moreover, Mbd3/NuRD directly regulates expression of pluripotency genes in ESCs to modulate transcriptional heterogeneity and maintain ESC lineage commitment [14].…”

Section: Introductionmentioning

confidence: 99%

NuRD Blocks Reprogramming of Mouse Somatic Cells into Pluripotent Stem Cells

et al. 2013

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Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of a defined set of transcription factors requires epigenetic changes in pluripotency genes. Nuclear reprogramming is an inefficient process and the molecular mechanisms that reset the epigenetic state during iPSC generation are largely unknown. Here, we show that downregulation of the nucleosome remodeling and deacetylation (NuRD) complex is required for efficient reprogramming. Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs by establishing heterochromatic features and silencing embryonic stem cell-specific marker genes, including Oct4 and Nanog. Depletion of Mbd3, on the other hand, improves reprogramming efficiency and facilitates the formation of pluripotent stem cells that are capable of generating viable chimeric mice, even in the absence of c-Myc or Sox2. The results establish Mbd3/NuRD as an important epigenetic regulator that restricts the expression of key pluripotency genes, suggesting that drug-induced downregulation of Mbd3/ NuRD may be a powerful means to improve the efficiency and fidelity of reprogramming.

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“…Briefly, DNA methylation serves as a signal to recruit the methyl CpG-binding domain (MBD) family including MeCP2, MBD1, MBD2, MBD3, and MBD4 [2,61,62]. The MBD proteins can recruit histone deacetylases, which are key to many gene silencing protein complexes [2,[63][64][65][66]. Importantly, all three biologically active DNMTs also bind these enzymes [67][68][69].…”

Section: Dna Methylationmentioning

confidence: 99%

Cancer epigenetics: linking basic biology to clinical medicine

2011

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Cancer evolution at all stages is driven by both epigenetic abnormalities as well as genetic alterations. Dysregulation of epigenetic control events may lead to abnormal patterns of DNA methylation and chromatin configurations, both of which are critical contributors to the pathogenesis of cancer. These epigenetic abnormalities are set and maintained by multiple protein complexes and the interplay between their individual components including DNA methylation machinery, histone modifiers, particularly, polycomb (PcG) proteins, and chromatin remodeling proteins. Recent advances in genome-wide technology have revealed that the involvement of these dysregulated epigenetic components appears to be extensive. Moreover, there is a growing connection between epigenetic abnormalities in cancer and concepts concerning stem-like cell subpopulations as a driving force for cancer. Emerging data suggest that aspects of the epigenetic landscape inherent to normal embryonic and adult stem/ progenitor cells may help foster, under the stress of chronic inflammation or accumulating reactive oxygen species, evolution of malignant subpopulations. Finally, understanding molecular mechanisms involved in initiation and maintenance of epigenetic abnormalities in all types of cancer has great potential for translational purposes. This is already evident for epigenetic biomarker development, and for pharmacological targeting aimed at reversing cancerspecific epigenetic alterations.

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The Dermatomyositis-Specific Autoantigen Mi2 Is a Component of a Complex Containing Histone Deacetylase and Nucleosome Remodeling Activities

Cited by 746 publications

References 59 publications

Identification of mRNAs differentially-expressed between benign and malignant breast tumour cells

Identification of mRNAs differentially-expressed between benign and malignant breast tumour cells

NuRD Blocks Reprogramming of Mouse Somatic Cells into Pluripotent Stem Cells

Cancer epigenetics: linking basic biology to clinical medicine

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