NURD, a Novel Complex with Both ATP-Dependent Chromatin-Remodeling and Histone Deacetylase Activities

Xue, Yutong; Wong, Jiemin; Moreno, G. Tony; Young, Mary K.; Côté, Jacques; Wang, Weidong

doi:10.1016/s1097-2765(00)80299-3

Cited by 894 publications

(791 citation statements)

References 51 publications

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“…(13) MTA1 is a subunit of the nuclear remodeling and deacetylation (NuRD) complex, which is associated with chromatin remodeling and histone deacetylase activity, leading to transcriptional regulation of specific genes. (29,30) Qian et al have reported recently that the use of chromatin remodeling agents, such as histone deacetylase All data are presented as mean ± standard deviation. inhibitor NVP-LAQ824, inhibits angiogenesis and has a greater antitumor effect in combination with the vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ ZK222584.…”

Section: Discussionmentioning

confidence: 99%

MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers

et al. 2006

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F emale breast cancer is a major public health problem, with more than 1 000 000 cases occurring worldwide annually. (1) Despite major advances that have been made in understanding the biological and clinical nature of the disease, the therapeutic problem persists. Therefore, identification of novel breast cancer biomarkers could be utilized as possible therapeutic targets or prognostic predictors that would contribute to the advancement of breast cancer treatment.Metastasis associated antigen 1 (MTA1) was originally identified by differential screening of a cDNA library from highly metastatic and non-metastatic rat mammary adenocarcinoma cell lines. (2)(3)(4) The expression level is estimated to be four-fold higher in the highly metastatic cell line MTLn3 than in the non-metastatic cell line MTC4. (2) The mRNA expression level of the human homolog of this gene is approximately four-times higher in a metastatic cell line (MDA-MB-231) than in a non-invasive and non-metastatic cell line (MDA-MB-468) in nude mice. (2) MTA1 is expressed physiologically at low levels in all normal tissue, except the testis. (2) Several studies have identified various roles for MTA1 in normal mammary gland development and human breast cancer progression, including cell proliferation and invasiveness. A study with MTA1 transgenic mice reveals that MTA1 dysregulation in mammary epithelium causes increased cell proliferation, hyper-branched ductal structure formation and precocious development, and results in the development of hyperplastic nodules and mammary gland tumors in virgin mice. (5) The growth of human MDA-MB-231 breast cancer cells is inhibited after treatment with MTA1 antisense phosphorothioate oligonucleotides. (6) MTA1 overexpression in non-invasive breast cancer MCF-7 cells yields larger colony formation in soft agar, augmented colony formation, as well as increased invasiveness in a Boyden chamber assay. (7) Thus, MTA1 may play an important role in tumorigenesis and tumor aggressiveness. However, the role of MTA1 in surgically resected breast cancer tissue with its clinicopathological parameters has not been investigated to date. Therefore, we analyzed the relationship between MTA1 expression and variable clinicopathological features.Tumor microenvironment is known to play an active role in tumor progression through adhesion molecules, angiogenesis and stromal host cells. (8)(9)(10) Previous experimental studies highlight the role of angiogenesis in tumor progression, such as tumor growth and blood-borne metastasis. (11,12) In breast cancer, the overall results of reported studies suggest that human breast cancer is an angiogenic-dependent tumor, and anti-angiogenic therapy may be beneficial for breast cancer patients. (13,14) Therefore, we analyzed the possible role of MTA1 in tumor angiogenesis of breast cancer by counting intratumoral microvessels, which is widely used to estimate tumor angiogenesis. (15) In the present study, we report a statistically significant correlation between MTA1 gene expression and increased...

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Section: Discussionmentioning

confidence: 99%

MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers

et al. 2006

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“…HDAC1 and HDAC2 are mainly found associated in the same molecular complexes with Mi2/ NURD (nucleosome remodelling and histone deacetylase), SIN3A and Co-REST, whereas HDAC3 is found in a different complex (the nuclear co-receptor (NCOR)/ silencing mediator for retinoid and thyroid hormone receptors (SMRT) complex) [126][127][128][129][130][131][132][133] . HDAC6 has been found in cytoplasmic complexes with proteins involved in the ubiquitin signalling pathway 134 .…”

Section: Box 1 | Histone Deacetylase Complexesmentioning

confidence: 99%

Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer

2006

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| Histone deacetylases (HDACs) are considered to be among the most promising targets in drug development for cancer therapy, and first-generation histone deacetylase inhibitors (HDACi) are currently being tested in phase I/II clinical trials. A wide-ranging knowledge of the role of HDACs in tumorigenesis, and of the action of HDACi, has been achieved. However, several basic aspects are not yet fully understood. Investigating these aspects in the context of what we now understand about HDACi action both in vitro and in vivo will further improve the design of optimized clinical protocols.Histone deacetylases (HDACs) have been intensively scrutinized over the past few years for two main reasons. First, they have been linked mechanistically to the pathogenesis of cancer, as well as several other diseases. Second, small-molecule HDAC inhibitors (HDACi) exist that have the capacity to interfere with HDAC activity and can therefore achieve significant biological effects in preclinical models of cancer. These findings justified the introduction of HDACi into clinical trials. These initial clinical trials have just ended and show encouraging results. At this stage it is crucial to evaluate whether our current knowledge on the mechanisms of tumorigenesis that are linked to HDACs, and on the mechanisms of tumour sensitivity to HDACi, is firm enough to improve the design of further clinical trials. Recent structural and chemical data have emerged that will help in the design of novel HDACi with more desirable properties than the existing ones. However, key areas of investigation that might help to further illuminate the design of successful HDACi-based cancer therapy remain poorly explored. Novel findings indicate that our understanding of how HDACi work will probably change significantly, establishing a new paradigm in the field of intelligent drug design with broad implications for the design of targeted therapies in cancer and possibly other diseases.HDACs: enzymes looking for substrate(s) Four HDAC classes have been identified (FIG. 1a). One of them (class 3 or the so-called sirtuins, from the yeast protein Sir2) constitutes a structurally unrelated, NADdependent subfamily, and will not be considered here; neither will the class 3-specific HDACi, which are less characterized than those for the other classes 1 .An extensive phylogenetic analysis of HDACs has been performed 2,3 . HDACs are members of an ancient enzyme family found in animals, plants, fungi and bacteria. It is thought that HDACs evolved in the absence of histone proteins. Indeed, eukaryotic HDACs can deacetylate non-histone as well as histone substrates, and some HDACs reside in the cytoplasm (where histones are synthesized and acetylated for proper assembly, without the intervention of HDACs) and in mitochondria (where histones are absent).Are HDACs, then, truly HDACs 4 ? We postulate that key HDAC substrates might not be histones, but instead belong to the growing list of acetylated non-histone proteins (FIG. 1b and Supplementary information S1 ...

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“…The homologues of PKL in animal cells, CHD3 remodelers, form the Mi-2/NuRD complex with other proteins to interact with chromatin and histones to regulate transcriptional events (Ramirez and Hagman, 2009;Xue et al, 1998). To elucidate the mechanisms of how PKL regulates gene expression, we generated polyclonal antibodies against PKL for ChIP-qPCR assay.…”

Section: Pkl Binds To the Multiple Regions Of Lfy And Pkl Facilitatesmentioning

confidence: 99%

CHD3 chromatin-remodeling factor PICKLE regulates floral transition partially via modulating LEAFY expression at the chromatin level in Arabidopsis

Liang

et al. 2016

Sci. China Life Sci.

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PICKLE (PKL), a putative CHD3 chromatin remodeling factor, has been suggested to be involved in multiple processes in Arabidopsis. Here, we confirmed the late-flowering phenotype caused by pkl mutation with pkl mutants in two different ecotypes, and investigated the possible mechanisms that account for PKL regulation of flowering time. Quantitative RT-PCR and RNA-seq assays showed that expression of the LEAFY gene (LFY) and a number of LFY-regulated floral homeotic genes were down-regulated in seedlings of the pkl mutants. As predicted, overexpression of LFY restored normal flowering time of pkl mutants. Our results suggest that PKL may be involved in regulating flowering time via LFY expression. To uncover the underlying mechanism, ChIP-PCR using anti-PKL was performed on materials from three developmental stages of seedlings. Our results showed that PKL associated with the genomic sequences of LFY, particularly at 10-day and 25-day after germination. We also showed that loss of PKL affected H3K27me3 level at the promoter of LFY. Taken together, our data suggest that transcriptional regulation of LFY at the chromatin level by PKL may at least partially account for the late-flowering phenotype of pkl mutants. chromatin-remodeling factor, PICKLE, floral transition, LEAFY, Arabidopsis Citation:Fu, X., Li, C., Liang, Q., Zhou, Y., He, H., and Fan, L.M. (2016). CHD3 chromatin-remodeling factor PICKLE regulates floral transition partially via modulating LEAFY expression at the chromatin level in Arabidopsis. Sci China Life Sci 59, 516 -528.

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NURD, a Novel Complex with Both ATP-Dependent Chromatin-Remodeling and Histone Deacetylase Activities

Cited by 894 publications

References 51 publications

MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers

MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers

Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer

CHD3 chromatin-remodeling factor PICKLE regulates floral transition partially via modulating LEAFY expression at the chromatin level in Arabidopsis

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