Nuclear Receptor Mediated Gene Regulation through Chromatin Remodeling and Histone Modifications

Kishimoto, Megumi; Fujiki, Ryoji; Takezawa, Shinichiro; Sasaki, Yuya; Nakamura, Takashi; Yamaoka, Kaoru; Kitagawa, Hirochika; Kato, Shigeaki

doi:10.1507/endocrj.53.157

Cited by 80 publications

(67 citation statements)

References 144 publications

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“…Chromatin remodelers function as multisubunit complexes and include ATPase catalytic subunits. Four family complexes (SWI/SNF, ISWI, WINAC, NURD) are thought to be transcriptional co-regulators for NRs (12).…”

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confidence: 99%

Double PHD Fingers Protein DPF2 Recognizes Acetylated Histones and Suppresses the Function of Estrogen-related Receptor α through Histone Deacetylase 1

Matsuyama

Takada

Yokoyama

et al. 2010

Journal of Biological Chemistry

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Estrogen-related receptor ␣ (ERR␣) is a member of the nuclear receptor superfamily and regulates many physiological functions, including mitochondrial biogenesis and lipid metabolism. ERR␣ enhances the transactivation function without endogenous ligand by associating with coactivators such as peroxisome proliferator-activated receptor ␥ coactivator 1 ␣ and ␤ (PGC-1␣ and -␤) and members of the steroid receptor coactivator family. However, the molecular mechanism by which the transactivation function of ERR␣ is converted from a repressive state to an active state is poorly understood. Here we used biochemical purification techniques to identify ERR␣-associated proteins in HeLa cells stably expressing ERR␣. Interestingly, we found that double PHD fingers protein DPF2/BAF45d suppressed PGC-1␣-dependent transactivation of ERR␣ by recognizing acetylated histone H3 and associating with HDAC1. DPF2 directly bound to ERR␣ and suppressed the transactivation function of nuclear receptors such as androgen receptor. DPF2 was recruited to ERR target gene promoters in myoblast cells, and knockdown of DPF2 derepressed the level of mRNA expressed by target genes of ERR␣. These results show that DPF2 acts as a nuclear receptor-selective co-repressor for ERR␣ by associating with both acetylated histone H3 and HDAC1.Nuclear receptors (NRs) 3 play pivotal roles during the development of vertebrates and in diverse physiological events in adults (1, 2). NRs constitute a gene superfamily and act as transcription factors. For most members of the NR superfamily, the transcriptional function is dependent on binding of lipophilic ligands such as steroid hormones and fat-soluble vitamins. The other subset of NRs is considered an orphan receptor, as physiologically relevant ligands remain to be identified. Orphan receptors are constitutively active or repressive transcription factors; however, their potency in transcriptional regulation appears to be dependent on cell types and the promoter context (3).For ligand-dependent transcriptional controls by nuclear steroid/vitamin receptors, several distinct classes of transcriptional co-regulators-co-regulator complexes are indispensable in addition to basic transcription machinery to reorganize chromatin state (4). Transcriptional co-regulators for NRs can be divided into two classes in terms of chromatin reorganization (5-7). One class consists of histone-modifying enzymes that reversibly modify the N-terminal tails of histone proteins (8, 9). For example, acetylation and methylation at histone H3K4 and H3K36 are chromatin-activating modifications and support transcriptional activation by NRs (8, 10, 11). In contrast, transcriptional repression by NRs is coupled with inactivating modifications like deacetylation and methylation at histone H3K9 and H3K27. Accordingly, cognate histone modifying enzymes serve as NR co-regulators.The other class of transcriptional co-regulators are chromatin remodeling factors that directly reorganize nucleosomal arrays through ATP hydrolysis (11). Chromatin remod...

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confidence: 99%

Double PHD Fingers Protein DPF2 Recognizes Acetylated Histones and Suppresses the Function of Estrogen-related Receptor α through Histone Deacetylase 1

Matsuyama

Takada

Yokoyama

et al. 2010

Journal of Biological Chemistry

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“…Like other nuclear receptors, VDR serves as a ligand-dependent transcription factor that requires distinct classes of co-regulators and multiprotein co-regulator complexes to initiate D3-induced chromatin reorganization (18). These complexes appear to modify chromatin configuration by controlling nucleosomal rearrangement and enzyme-catalyzed modifications of histone tails (19,20). As for VDR, many types of co-regulator complexes have been identified thus far, including p160 family histone-acetylating complexes, DRIP-TRAP complexes, and ATP-dependent chromatin remodeling complexes (21,22).…”

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confidence: 99%

Phosphorylation of Williams Syndrome Transcription Factor by MAPK Induces a Switching between Two Distinct Chromatin Remodeling Complexes

Oya

Yokoyama

Yamaoka

et al. 2009

Journal of Biological Chemistry

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Changes in the environment of a cell precipitate extracellular signals and sequential cascades of protein modification and elicit nuclear transcriptional responses. However, the functional links between intracellular signaling-dependent gene regulation and epigenetic regulation by chromatin-modifying proteins within the nucleus are largely unknown. Here, we describe novel epigenetic regulation by MAPK cascades that modulate formation of an ATPdependent chromatin remodeling complex, WINAC (WSTF Including Nucleosome Assembly Complex), an SWI/SNF-type complex containing Williams syndrome transcription factor (WSTF). WSTF, a specific component of two chromatin remodeling complexes (SWI/SNF-type WINAC and ISWI-type WICH), was phosphorylated by the stimulation of MAPK cascades in vitro and in vivo. Ser-158 residue in the WAC (WSTF/Acf1/cbpq46) domain, located close to the N terminus of WSTF, was identified as a major phosphorylation target. Using biochemical analysis of a WSTF mutant (WSTF-S158A) stably expressing cell line, the phosphorylation of this residue (Ser-158) was found to be essential for maintaining the association between WSTF and core BAF complex components, thereby maintaining the ATPase activity of WINAC. WINAC-dependent transcriptional regulation of vitamin D receptor was consequently impaired by this WSTF mutation, but the recovery from DNA damage mediated by WICH was not impaired. Our results suggest that WSTF serves as a nuclear sensor of the extracellular signals to fine-tune the chromatin remodeling activity of WINAC. WINAC mediates a previously unknown MAPK-dependent step in epigenetic regulation, and this MAPK-dependent switching mechanism between the two functionally distinct WSTF-containing complexes might underlie the diverse functions of WSTF in various nuclear events.

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“…Sirt1 maintains the DNA to prevent gene modification of various genes including CYP 450 enzymes [72] and allows rapid metabolism of xenobiotics that enter the organism. In under developed countries urbanization and Western diet changes involve Sirt 1dysregulation caused by alterations in transcriptional regulators and modification of chromatin that contribute to endocrine abnormalities such as insulin resistance, NAFLD and energy balance disorders [73][74][75][76][77][78][79].…”

Section: Gene Environment Interactions Induce Epigenetic Alterations mentioning

confidence: 99%

Increased Risk for Obesity and Diabetes with Neurodegeneration in Developing Countries

Martins

2014

J Mol Genet Med

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Nuclear Receptor Mediated Gene Regulation through Chromatin Remodeling and Histone Modifications

Cited by 80 publications

References 144 publications

Double PHD Fingers Protein DPF2 Recognizes Acetylated Histones and Suppresses the Function of Estrogen-related Receptor α through Histone Deacetylase 1

Double PHD Fingers Protein DPF2 Recognizes Acetylated Histones and Suppresses the Function of Estrogen-related Receptor α through Histone Deacetylase 1

Phosphorylation of Williams Syndrome Transcription Factor by MAPK Induces a Switching between Two Distinct Chromatin Remodeling Complexes

Increased Risk for Obesity and Diabetes with Neurodegeneration in Developing Countries

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