The human Mi-2/NuRD complex and gene regulation

Denslow, Sheri; Wade, Paul A.

doi:10.1038/sj.onc.1210611

Cited by 412 publications

(436 citation statements)

References 68 publications

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“…HDAC1 and HDAC2 lack a DNA-binding domain, as do all deacetylases, and execute their function by interacting with transcription factors as either homo-or heterodimers, or being part of multi-component repressor complexes. 8,9 The best characterized HDAC1/2-containing complexes in mammals are the SIN3 co-repressor complex, 23 nucleosome remodeling and deacetylase (NuRD) complex, 24 CoREST complex, 25 Nanog and Oct4 (POU5F1)-associated deacetylase complex that is specifically found in embryonic stem (ES) cells, 26 and PRC2 complex. 27 The ubiquitous expression, high deacetylase activity toward common substrates and high homology between HDAC1 and HDAC2 suggest that each could compensate for loss of function of the other.…”

Section: Structure and Complexes Of Mammalian Hdac1 And Hdac2mentioning

confidence: 99%

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

Schultz

2016

Cell Death Differ

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Oocyte and preimplantation embryo development entail dynamic changes in chromatin structure and gene expression, which are regulated by a number of maternal and zygotic epigenetic factors. Histone deacetylases (HDACs), which tighten chromatin structure, repress transcription and gene expression by removing acetyl groups from histone or non-histone proteins. HDAC1 and HDAC2 are two highly homologous Class I HDACs and display compensatory or specific roles in different cell types or in response to different stimuli and signaling pathways. We summarize here the current knowledge about the functions of HDAC1 and HDAC2 in regulating histone modifications, transcription, DNA methylation, chromosome segregation, and cell cycle during oocyte and preimplantation embryo development. What emerges from these studies is that although HDAC1 and HDAC2 are highly homologous, HDAC2 is more critical than HDAC1 for oocyte development and reciprocally, HDAC1 is more critical than HDAC2 for preimplantation development. In eukaryotes, DNA is organized into a highly ordered nucleoprotein assembly called chromatin, whose fundamental unit is the nucleosome. The nucleosome consists of 146 bp of DNA wrapped around a histone core comprised of two molecules each of histones H2A, H2B, H3 and H4. Histone H1 is bound to linker DNA between nucleosomes. 1,2 Histones are subject to multiple post-translational modifications (PTMs), including acetylation, methylation, ubiquitylation, phosphorylation, and sumoylation. These PTMs determine open and closed chromatin conformations, which, in turn, regulate the differential access and recruitment of transcription factors and other regulatory chromatin-binding proteins to DNA. 3-5 Among these histone modifications, histone acetylation is the most well-studied modification, which occurs at the ε-amino groups of evolutionarily conserved lysine residues located at the N termini. Although all core histones are acetylated in vivo, modifications of histones H3 and H4 are more extensively characterized than those of H2A and H2B. Abbreviations: HDAC, histone deacetylase; HAT, histone acetyl transferase; PTM, post-translational modification; KDAC, lysine deacetylase; TSA, trichostatin A; NAD + , nicotinamide adenine dinucleotide; HAD, HDAC association domain ; GVBD, germinal vesicle breakdown; ChIP-seq, chromatin immunoprecipitation sequencing; TFIID, transcription factor II D; YY1, yin yang 1; Pol II CTD S2, serine 2 within the RNApolymerase II C-terminal domain; H3K4, lysine 4 of histone 3; H3K9, lysine 9 of histone 3; H4K16, lysine 16 of histone 4; SIRT, NAD-dependent deacetylase sirtuin; TBP2, TATA-binding protein 2; DNMT, DNA methyltransferases; RBAP46, retinoblastoma binding protein P46; RNAi, RNA interference; aa, amino acidic; BrUTP, 5-Bromouridine 5′-triphosphate; qRT-PCR, quantitative reverse transcription polymerase chain reaction;

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Section: Structure and Complexes Of Mammalian Hdac1 And Hdac2mentioning

confidence: 99%

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

Schultz

2016

Cell Death Differ

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“…The Mi2/nucleosome remodeling and deacetylase (Mi2/NuRD) complex consists of multiple components and couples both histone deacetylase (HDAC) and chromatin-remodeling ATPase activities [20]. Its Mi2α or Mi2β component contains ATPase activity that is stimulated by chromatin but not by free DNA or histones [20].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Its Mi2α or Mi2β component contains ATPase activity that is stimulated by chromatin but not by free DNA or histones [20]. Mi2 is known to facilitate nucleosome mobility through a sliding mechanism [20][21][22]. The combined activities of HDAC and ATPase in the Mi2/NuRD complex result in the generation of densely packed, hypoacetylated nucleosomes for gene silencing [20].…”

Section: Introductionmentioning

confidence: 99%

“…Mi2 is known to facilitate nucleosome mobility through a sliding mechanism [20][21][22]. The combined activities of HDAC and ATPase in the Mi2/NuRD complex result in the generation of densely packed, hypoacetylated nucleosomes for gene silencing [20]. The RbAp46 and/or RbAp48 subunits were originally identified as proteins associated with the retinoblastoma (Rb) tumor suppressor [23], and they may function as structural proteins that provide interactive interfaces for other components of the Mi2/NuRD complex [20,24,25].…”

Section: Introductionmentioning

confidence: 99%

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The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis

et al. 2010

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The epithelial-mesenchymal transition (EMT) converts epithelial tumor cells into invasive and metastatic cancer cells, leading to mortality in cancer patients. Although TWIST is a master regulator of EMT and metastasis for breast and other cancers, the mechanisms responsible for TWIST-mediated gene transcription remain unknown. In this study, purification and characterization of the TWIST protein complex revealed that TWIST interacts with several components of the Mi2/nucleosome remodeling and deacetylase (Mi2/NuRD) complex, MTA2, RbAp46, Mi2 and HDAC2, and recruits them to the proximal regions of the E-cadherin promoter for transcriptional repression. Depletion of these TWIST complex components from cancer cell lines that depend on TWIST for metastasis efficiently suppresses cell migration and invasion in culture and lung metastasis in mice. These findings not only provide novel mechanistic and functional links between TWIST and the Mi2/NuRD complex but also establish new essential roles for the components of Mi2/NuRD complex in cancer metastasis.

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Epigenetic reactivation of LINE‐1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cells

Bojang

Ramos

2018

Molecular Oncology

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Long interspersed nuclear element‐1 (LINE‐1 or L1) reactivation is linked to poor prognosis in non‐small‐cell lung carcinoma (NSCLC), but the molecular bases of this response remain largely unknown. In this report, we show that challenge of human bronchial epithelial cells (HBECs) with the lung carcinogen, benzo(a)pyrene (BaP), shifted the L1 promoter from a heterochromatic to euchromatic state through disassembly of the nucleosomal and remodeling deacetylase (NuRD) complex. Carcinogen challenge was also associated with partial displacement of constituent proteins from the nuclear to the cytoplasmic compartment. Disruption of NuRD corepression by genetic ablation or carcinogen treatment correlated with accumulation of L1 mRNA and proteins. Mi2β bound directly to the L1 promoter to effect retroelement silencing, and this response required the DNA‐ and ATPase‐binding domains of Mi2β. Sustained expression of L1 in HBECs was tumorigenic in a human–SCID mouse xenograft model, giving rise to tumors that regressed over time. Together, these results show that functional modulation of the NuRD constituent proteins is a critical molecular event in the activation of L1 retrotransposon. L1 expression creates a microenvironment in HBECs that is conducive to neoplasia and malignant transformation.

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The human Mi-2/NuRD complex and gene regulation

Cited by 412 publications

References 68 publications

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis

Epigenetic reactivation of LINE‐1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cells

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