Expression of tyrosine hydroxylase is epigenetically regulated in neural stem cells

Yang, Jae Won; Choi, Eun Yang; Park, Mi Jung; Lee, Myung Ae

doi:10.1016/j.bbrc.2011.09.141

Cited by 12 publications

(13 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: The Generation Of Mature Mdda Neurons: Epigenenetic Control mentioning

confidence: 81%

“…Studies have shown that a repressive regulatory region upstream of the putative Th promoter is fully methylated in NSCs, whereas several CpGs may be demethylated in Th-positive cells. In line with this, an unmethylated CpG (−1868 of the Th transcription start site) has been located within a binding site of the methylated CpG-binding proteins Mbd2 and MeCP2, which recruit repressors and may act independently of Rest, serving as an additional repressive element Yang et al, 2011).Interestingly, a role for PcG group (and PcG group-like) proteins in Th gene regulation has also been described. In Caenorhabditis elegans, the PcG-like proteins SOP-2 and SOR-3 specify and maintain neuronal fate by regulating the expression of DA metabolic enzymes, including the C. elegans homolog of tyrosine hydroxylase (CAT-2) (Yang et al, 2007).…”

mentioning

confidence: 74%

“…In neural stem cells (NSCs), the neurorestrictive silencer factor repressor element 1 silencing transcription factor (NRSF; also known as Rest), a well-established repressor of >2000 neuronal genes, has been reported to repress the expression of two microRNAs, miR-9 and, in particular, miR-124, in NSCs (Conaco et al, 2006), thereby preventing NSCs from maturing or exiting a self-renewal state (Yoo et al, 2011). In vitro studies suggested that the Th locus is regulated by a proximal cis-regulatory mechanism that involves Rest, the co-repressor coREST (also known as Rcor2) and HDAC recruitment Yang et al, 2011) (Fig. 4A).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Epigenetic mechanisms in the development and maintenance of dopaminergic neurons

et al. 2013

View full text Add to dashboard Cite

SummaryMesodiencephalic dopaminergic (mdDA) neurons are located in the ventral mesodiencephalon and are involved in psychiatric disorders and severely affected in neurodegenerative diseases such as Parkinson's disease. mdDA neuronal development has received much attention in the last 15 years and many transcription factors involved in mdDA specification have been discovered. More recently however, the impact of epigenetic regulation has come into focus, and it's emerging that the processes of histone modification and DNA methylation form the basis of genetic switches that operate during mdDA development. Here, we review the epigenetic control of mdDA development, maturation and maintenance. As we highlight, epigenetic mechanisms play a pivotal role in all of these processes and the knowledge gathered from studying epigenetics in these contexts may aid our understanding of mdDA-related pathologies. Key words: Brain, Development, Dopamine, Epigenetics, Gene regulation, Midbrain IntroductionIf you turn this page, both the decision you make and the action that you carry out are significantly influenced by the amount of dopamine (DA; see Glossary, Box 1) released from dopaminergic neurons within your brain. Mesodiencephalic dopaminergic (mdDA) neurons located in the substantia nigra pars compacta (SNc; see Glossary, Box 1), in particular, are essential for motor functions whereas mdDA neurons of the ventral tegmental area (VTA; see Glossary, Box 1) and the retrorubal field (RRF; see Glossary, Box 1) are involved in the regulation of emotions and reward . Notably, severe loss of SNc mdDA neurons is a pathological hallmark of Parkinson's disease (PD) (Sulzer, 2007). By contrast, mdDA neurons in the VTA and RRF, which remain intact in PD, are part of the mesocorticolimbic system (see Glossary, Box 1), in which defective DA neurotransmission has been implicated in the development of drug addiction, depression and schizophrenia (Nestler, 2000). Given their involvement in neurodegenerative diseases and psychiatric disorders, mdDA neurons have been studied intensively in recent years.In the last two decades, a variety of molecular approaches have revealed factors that are specific for mdDA neuronal subsets or that guide their spatial organization ; recently, a pathway that molecularly distinguishes SNc DA neurons from those located in the VTA was identified (Jacobs et al., 2011). In addition to molecular profiling of DA neurons, however, a second level of complexity has been added by the rapidly emerging field of epigenetics, which has provided new insights into the origin and maintenance of distinctive gene expression patterns in mdDA neurons. Current definitions of epigenetics often emphasize the heritability of changes in gene expression throughout cell divisions that are not due to alterations in DNA sequence. However, perhaps a more appropriate definition of epigenetics, especially when applying this term to mature neurons that cannot divide, is postulated by Adrian Bird: 'The structural adaptation of chromosomal regio...

show abstract

Section: The Generation Of Mature Mdda Neurons: Epigenenetic Control mentioning

confidence: 81%

mentioning

confidence: 74%

mentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic mechanisms in the development and maintenance of dopaminergic neurons

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Further investigations of which phosphorylated site of TH is involved in the regulation of TH expression in response to the treatment with reserpine is required to clarify the mechanisms of TH downregulation. Likewise, epigenetic studies could also help to clarify how such cellular oxidative imbalance would modulate the expression of TH (Yang et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson’s Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and α-Synuclein Expression

Leão

Meurer

Silva

et al. 2017

Front. Aging Neurosci.

View full text Add to dashboard Cite

Reserpine is an irreversible inhibitor of vesicular monoamine transporter-2 (VMAT2) used to study Parkinson’s disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low-dose of reserpine was proposed as a progressive model of PD. Rats under this treatment show progressive catalepsy behavior, oral movements and spontaneous motor activity decrement. In parallel, compared to Wistar rats, spontaneously hypertensive rats (SHR) are resistant to acute reserpine-induced oral dyskinesia. We aimed to assess whether SHR would present differential susceptibility to repeated reserpine-induced deficits in the progressive model of PD. Male Wistar and SHR rats were administered 15 subcutaneously (s.c.) injections of reserpine (0.1 mg/kg) or vehicle, every other day and motor activity was assessed by the catalepsy, oral movements and open field tests. Only reserpine-treated Wistar rats presented increased latency to step down in the catalepsy test and impaired spontaneous activity in the open field. On the other hand, there was an increase in oral movements in both reserpine-treated strains, although with reduced magnitude and latency to instauration in SHR. After a 15-day withdrawn period, both strains recovered from motor impairment, but SHR animals expressed reduced latencies to reach control levels. Finally, we performed immunohistochemistry for tyrosine hydroxylase (TH) and α-synuclein (α-syn) 48 h after the last injection or 15 days after withdrawn. Reserpine-treated animals presented a reduction in TH and an increase in α-syn immunoreactivity in the substantia nigra and dorsal striatum (dSTR), which were both recovered after 15 days of withdraw. Furthermore, SHR rats were resistant to reserpine-induced TH decrement in the substantia nigra, and presented reduced immunoreactivity to α-syn in the dSTR relative to Wistar rats, irrespective of treatment. This effect was accompanied by increase of malondaldhyde (MDA) in the striatum of reserpine-treated Wistar rats, while SHR presented reduced MDA in both control and reserpine conditions relative to Wistar strain. In conclusion, the current results show that SHR are resilient to motor and neurochemical impairments induced by the repeated low-dose reserpine protocol. These findings indicate that the neurochemical, molecular and genetic differences in the SHR strain are potential relevant targets to the study of susceptibility to PD.

show abstract

“…Jacobs and colleagues (Jacobs et al, 2009b) have reported another epigenetic control mechanism mediated by the Nurr1 activator Pitx3, in which Pitx3 potentiates Nurr1-induced DA gene expression by releasing an Smrt (Ncor1 -Mouse Genome Informatics)-mediated repressor complex (Smrt/Sin3a/Hdac). In addition, Nrsf (Rest -Mouse Genome Informatics) and MeCP2 (Yang et al, 2011) have been suggested to be the central negative regulators of Th gene transcription during mDA neuron development, possibly by repressing Nurr1 actions (van Heesbeen et al, 2013). It remains to be seen whether all these repressor proteins form a large repressor complex, or if different combinations of the proteins are generated on different regions of the promoters or in different cellular contexts.…”

Section: Analysis Of Nurr1mentioning

confidence: 99%

Foxa2 acts as a co-activator potentiating expression of the Nurr1-induced DA phenotype via epigenetic regulation

Rhee

et al. 2014

Development

View full text Add to dashboard Cite

Understanding how dopamine (DA) phenotypes are acquired in midbrain DA (mDA) neuron development is important for bioassays and cell replacement therapy for mDA neuron-associated disorders. Here, we demonstrate a feed-forward mechanism of mDA neuron development involving Nurr1 and Foxa2. Nurr1 acts as a transcription factor for DA phenotype gene expression. However, Nurr1-mediated DA gene expression was inactivated by forming a protein complex with CoREST, and then recruiting histone deacetylase 1 (Hdac1), an enzyme catalyzing histone deacetylation, to DA gene promoters. Coexpression of Nurr1 and Foxa2 was established in mDA neuron precursor cells by a positive cross-regulatory loop. In the presence of Foxa2, the Nurr1-CoREST interaction was diminished (by competitive formation of the Nurr1-Foxa2 activator complex), and CoRESTHdac1 proteins were less enriched in DA gene promoters. Consequently, histone 3 acetylation (H3Ac), which is responsible for open chromatin structures, was strikingly increased at DA phenotype gene promoters. These data establish the interplay of Nurr1 and Foxa2 as the crucial determinant for DA phenotype acquisition during mDA neuron development.KEY WORDS: Foxa2, Nurr1, Midbrain dopamine neuron, Development, Neural precursor cell, Epigenetic control, CoREST, Hdac, Mouse INTRODUCTIONMidbrain dopamine (mDA) neurons play important roles in voluntary movement, emotion and reward-based behaviors. Dysfunction or degeneration of this neuronal subtype is related to major neuropsychiatric disorders such as Parkinson's disease (PD), schizophrenia and drug addiction. Owing to the pathophysiological implications, mDA neurons are the most extensively studied cells. A molecular understanding of mDA neuron development is of high clinical interest as replacing this cell population in diseased brains is considered to be one of the most promising therapeutic approaches for PD (Deierborg et al., 2008;Morizane et al., 2008). In addition, developmental information can be exploited to establish optimal bioassays for mDA neuron-related disorders. mDA neurons arise from floor plate cells at the ventral midline of the embryonic midbrain (Bonilla et al., 2008;Ono et al., 2007). Sonic hedgehog (Shh), secreted initially by the notochord and later by floor plate cells, induces expression of forkhead family of winged-helix transcription factor 2 (Foxa2; also known as hepatocyte nuclear factor 3 beta), in the midbrain floor plate cells [mouse embryonic day (E) 8.5] (Ang et al., 1993;Monaghan et al., 1993;Placzek, 1995;Sasaki and Hogan, 1994;Sasaki et al., 1997). Foxa2 acts as a master regulator to induce expression of developmental factors specifying mDA neuron precursors such as Nurr1, Pitx3, Lmx1a, Msx1, neurogenin 2 and Mash1 (Ascl1 -Mouse Genome Informatics) (Ang, 2009;Ferri et al., 2007;Kittappa et al., 2007;Lee et al., 2010;Metzakopian et al., 2012). The early inductive role of Foxa2 is probably achieved by cooperation with the Wnt-Lmx1a/b regulatory loop from the isthmic organizer (Chung et al., 2009;Naka...

show abstract

Expression of tyrosine hydroxylase is epigenetically regulated in neural stem cells

Cited by 12 publications

References 28 publications

Epigenetic mechanisms in the development and maintenance of dopaminergic neurons

Epigenetic mechanisms in the development and maintenance of dopaminergic neurons

Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson’s Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and α-Synuclein Expression

Foxa2 acts as a co-activator potentiating expression of the Nurr1-induced DA phenotype via epigenetic regulation

Contact Info

Product

Resources

About