Regulation of human tyrosine hydroxylase gene by neuron-restrictive silencer factor

Kim, Soo Min; Yang, Jae Won; Park, Mi Jung; Lee, Joon-Kyu; Kim, Seung Up; Lee, Young Seek; Lee, Myung Ae

doi:10.1016/j.bbrc.2006.05.142

Cited by 39 publications

(28 citation statements)

References 37 publications

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“…2A). This is consistent with the result that mutation of the NESE-R site (including CpG 2) slightly increased TH promoter activity in HB1.F3 cells in our previous study [19]. Thus, there was good correlation between the methylation status around the NRSE-R site in the TH promoter and TH gene expression.…”

Section: Analysis Of Th Promoter Methylation Patternssupporting

confidence: 92%

“…While the NRSE-II region, which is proximal to the transcription start site, is involved in repression of TH via NRSF/REST, the region of the TH promoter between À2164 and À1210 bp, which includes the NRSE-R and NRSE-I sites, may repress TH expression in an NRSF/REST-independent manner [19]. The present study addressed the question: what are the regulatory elements in the À2164 to À1210 bp region that are involved in TH gene silencing in NSCs?…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study showed that the region between À2164 and À1210 bp in the TH promoter contains one or more silencing elements that represses TH gene transcription in NSCs but not in other cells (including DAergic neuron-like cells) [19]. Although this region contains two binding sites for the pan-neuronal repressors NRSF, NRSE-R and NRSE-I, mutation of these sites or treatment with the histone deacetylase inhibitor TSA has no effect on the transcriptional activity of TH promoter.…”

Section: Cell Type-specific Transcriptional Activities Of the Th Prommentioning

confidence: 99%

“…Specifically, both the NRSE-II site and a repressor region between À2164 and À1210 bp in the TH promoter act as cis-regulatory elements [19]. The silencing element in the À2164 and À1210 region represses TH expression in an NRSF-independent manner.…”

Section: Introductionmentioning

confidence: 99%

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Expression of tyrosine hydroxylase is epigenetically regulated in neural stem cells

Yang¹,

Choi²,

Park³

et al. 2011

Biochemical and Biophysical Research Communications

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Section: Analysis Of Th Promoter Methylation Patternssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Cell Type-specific Transcriptional Activities Of the Th Prommentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression of tyrosine hydroxylase is epigenetically regulated in neural stem cells

Yang¹,

Choi²,

Park³

et al. 2011

Biochemical and Biophysical Research Communications

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“…In addition to Mitf (22), another Wnt target gene with a potential role in NC fate determination is the RE-1 silencing transcription factor gene (REST) (55,81), a transcriptional repressor of neuron-specific genes, expressed in nonneuronal cells and neural progenitors (17,65). The repressor activity of REST suppresses expression of a wide network of neuronal genes, including those encoding tyrosine hydroxylase (TH) and dopamine-␤-hydroxylase (DBH) (39,40), both required for catecholamine synthesis. In addition, REST suppresses expression of Ash-1 (57), a proneural transcription factor required for SA lineage commitment (33,52).…”

mentioning

confidence: 99%

CtBP2 Downregulation during Neural Crest Specification Induces Expression of Mitf and REST, Resulting in Melanocyte Differentiation and Sympathoadrenal Lineage Suppression

Liang

Fekete

Andrisani

2011

Molecular and Cellular Biology

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Trunk neural crest (NC) cells differentiate to neurons, melanocytes, and glia. In NC cultures, cyclic AMP (cAMP) induces melanocyte differentiation while suppressing the neuronal sympathoadrenal lineage, depending on the signal intensity. Melanocyte differentiation requires activation of CREB and cAMP-dependent protein kinase A (PKA), but the role of PKA is not understood. We have demonstrated, in NC cultures, cAMP-induced transcription of the microphthalmia-associated transcription factor gene ( Mitf ) and the RE-1 silencing transcription factor gene ( REST ), both Wnt-regulated genes. In NC cultures and zebrafish, knockdown of the corepressor of Wnt-mediated transcription C-terminal binding protein 2 (CtBP2) but not CtBP1 derepressed Mitf and REST expression and enhanced melanocyte differentiation. cAMP in NC and B16 melanoma cells decreased CtBP2 protein levels, while inhibition of PKA or proteasome rescued CtBP2 degradation. Interestingly, knockdown of homeodomain-interacting protein kinase 2 (HIPK2), a CtBP stability modulator, increased CtBP2 levels, suppressed expression of Mitf, REST, and melanocyte differentiation, and increased neuronal gene expression and sympathoadrenal lineage differentiation. We conclude that cAMP/PKA via HIPK2 promotes CtBP2 degradation, leading to Mitf and REST expression. Mitf induces melanocyte specification, and REST suppresses neuron-specific gene expression and the sympathoadrenal lineage. Our studies identify a novel role for REST in NC cell differentiation and suggest cross talk between cAMP and Wnt signaling in NC lineage specification.

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Epigenetic Regulation Contributes to Urocortin-Enhanced Midbrain Dopaminergic Neuron Differentiation

et al. 2015

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The production of midbrain dopaminergic (mDA) neurons requires precise extrinsic inductive signals and intrinsic transcriptional cascade at a specific time point in development. Urocortin (UCN) is a peptide of the corticotropin-releasing hormone family that mediates various responses to stress. UCN was first cloned from adult rat midbrain. However, the contribution of UCN to the development of mDA neurons is poorly understood. Here, we show that UCN is endogenously expressed in the developing ventral midbrain (VM) and its receptors are exhibited in Nurr1 1 postmitotic mDA precursors and TH 1 neurons, suggesting possible roles in regulating their terminal differentiation. UCN treatment increased DA cell numbers in rat VM precursor cultures by promoting the conversion of Nurr1 1 precursors into DA neurons. Furthermore, neutralization of secreted UCN with anti-UCN antibody resulted in a reduction in the number of DA neurons. UCN induced an abundance of acetylated histone H3 and enhanced late DA regulator Nurr1, Foxa2, and Pitx3 expressions. Using pharmacological and RNA interference approaches, we further demonstrated that histone deacetylase (HDAC) inhibition and late transcriptional factors upregulation contribute to UCN-mediated DA neuron differentiation. Chromatin immunoprecipitation analyses revealed that UCN promoted histone acetylation of chromatin surrounding the TH promoter by directly inhibiting HDAC and releasing of methyl CpG binding protein 2-CoREST-HDAC1 repressor complex from the promoter, ultimately leading to an increase in Nurr1/coactivators-mediated transcription of TH gene. Moreover, UCN treatment in vivo also resulted in increased DA neuron differentiation. These findings suggest that UCN might contribute to regulate late mDA neuron differentiation during VM development. STEM CELLS

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Regulation of human tyrosine hydroxylase gene by neuron-restrictive silencer factor

Cited by 39 publications

References 37 publications

Expression of tyrosine hydroxylase is epigenetically regulated in neural stem cells

Expression of tyrosine hydroxylase is epigenetically regulated in neural stem cells

CtBP2 Downregulation during Neural Crest Specification Induces Expression of Mitf and REST, Resulting in Melanocyte Differentiation and Sympathoadrenal Lineage Suppression

Epigenetic Regulation Contributes to Urocortin-Enhanced Midbrain Dopaminergic Neuron Differentiation

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