The Mi-2/NuRD complex: A critical epigenetic regulator of hematopoietic development, differentiation and cancer

Ramírez, Julita; Hagman, James

doi:10.4161/epi.4.8.10108

Cited by 78 publications

(85 citation statements)

References 27 publications

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“…1D). Of the ;89 gene targets identified in the initial screen (Supplemental Table S1), we elected to focus on CHD4, a member of the nucleosome remodeling (NuRD) complex (Denslow and Wade 2007;Ramirez and Hagman 2009) shRNAs targeting CHD4 were identified in the RNAi screen, and CHD4 was recently implicated as a tumor suppressor in several female malignancies (Le Gallo et al 2012;Zhao et al 2013). Moreover, PEO1 cells expressing any of four unrelated CHD4 shRNAs displayed substantially increased colony survival following cisplatin treatment, similar to the BRCA2 revertant line C4-2 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Resistance to therapy in BRCA2 mutant cells due to loss of the nucleosome remodeling factor CHD4

et al. 2015

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Hereditary cancers derive from gene defects that often compromise DNA repair. Thus, BRCA-associated cancers are sensitive to DNA-damaging agents such as cisplatin. The efficacy of cisplatin is limited, however, by the development of resistance. One cisplatin resistance mechanism is restoration of homologous recombination (HR), which can result from BRCA reversion mutations. However, in BRCA2 mutant cancers, cisplatin resistance can occur independently of restored HR by a mechanism that remains unknown. Here we performed a genome-wide shRNA screen and found that loss of the nucleosome remodeling factor CHD4 confers cisplatin resistance. Restoration of cisplatin resistance is independent of HR but correlates with restored cell cycle progression, reduced chromosomal aberrations, and enhanced DNA damage tolerance. Suggesting clinical relevance, cisplatin-resistant clones lacking genetic reversion of BRCA2 show de novo loss of CHD4 expression in vitro. Moreover, BRCA2 mutant ovarian cancers with reduced CHD4 expression significantly correlate with shorter progression-free survival and shorter overall survival. Collectively, our findings indicate that CHD4 modulates therapeutic response in BRCA2 mutant cancer cells.

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Section: Resultsmentioning

confidence: 99%

Resistance to therapy in BRCA2 mutant cells due to loss of the nucleosome remodeling factor CHD4

et al. 2015

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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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“…The Mi-2/ NuRD core complex consists of ATPases of CHD3 (chromodomain helicase DNA-binding protein 3; also known as Mi-2␣) and CHD4 (also known as Mi-2␤); HDAC1 (histone deacetylase 1) and HDAC2; MBD2 (methyl-CpG-binding domain 2) and MBD3; MTA1 (metastasis-associated gene 1), MTA2, and MTA3; RBBP4 (retinoblastoma binding protein 4; also known as RbAp48) and RBBP7 (also known as RbAp46); and p66␣ and p66␤ (1-5). The NuRD complex is widely conserved in animal and plant species and has been shown to play important roles in gene expression regulation and development (6,7). Additionally, multiple lines of evidence show that the NuRD complex functions primarily in gene transcriptional repression through its association with diverse transcription factors (6,8).…”

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confidence: 99%

Structural Basis of Plant Homeodomain Finger 6 (PHF6) Recognition by the Retinoblastoma Binding Protein 4 (RBBP4) Component of the Nucleosome Remodeling and Deacetylase (NuRD) Complex

Zhang

et al. 2015

Journal of Biological Chemistry

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Background:The PHF6 gene is mutated in patients with Börjeson-Forssman-Lehmann syndrome, T-cell acute lymphoblastic leukemia, and acute myeloid leukemia. The PHF6 protein is a newly identified interactor with the NuRD complex. Results: The complex structure of the NoLS region of PHF6 bound to RBBP4 was solved. Conclusion: By interacting with the RBBP4 component, PHF6 associates with the NuRD complex. Significance: Association with the NuRD complex implicates a role for PHF6 in chromatin structure modulation and gene regulation.

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The Mi-2/NuRD complex: A critical epigenetic regulator of hematopoietic development, differentiation and cancer

Cited by 78 publications

References 27 publications

Resistance to therapy in BRCA2 mutant cells due to loss of the nucleosome remodeling factor CHD4

Resistance to therapy in BRCA2 mutant cells due to loss of the nucleosome remodeling factor CHD4

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

Structural Basis of Plant Homeodomain Finger 6 (PHF6) Recognition by the Retinoblastoma Binding Protein 4 (RBBP4) Component of the Nucleosome Remodeling and Deacetylase (NuRD) Complex

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