Effects of histone deacetylation inhibition on neuronal differentiation of embryonic mouse neural stem cells

Balasubramaniyan, Veerakumar; Boddeke, Erik; Bakels, Rob; Küst, B.M.; Kooistra, Susanne M.; Veneman, A.; Copray, Sjef

doi:10.1016/j.neuroscience.2006.08.082

Cited by 124 publications

(96 citation statements)

References 42 publications

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“…Furthermore, it has been shown that HDAC inhibitors induce differentiation of both embryonic and adult cortical neuronal progenitor cells to neurons specifically (7)(8)(9). The wide expression pattern of a number of HDACs in the developing brain suggests specific roles for individual HDACs in neuronal development (10), however, the broad inhibition of classical HDAC inhibitors has precluded the analysis of individual HDACs pharmacologically.…”

mentioning

confidence: 99%

Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Montgomery¹,

Hsieh²,

Barbosa³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

275

247

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The molecular mechanism by which neural progenitor cells commit to a specified lineage of the central nervous system remains unknown. We show that HDAC1 and HDAC2 redundantly control neuronal development and are required for neuronal specification. Mice lacking HDAC1 or HDAC2 in neuronal precursors show no overt histoarchitectural phenotypes, whereas deletion of both HDAC1 and HDAC2 in developing neurons results in severe hippocampal abnormalities, absence of cerebellar foliation, disorganization of cortical neurons, and lethality by postnatal day 7. These abnormalities in brain formation can be attributed to a failure of neuronal precursors to differentiate into mature neurons and to excessive cell death. These results reveal redundant and essential roles for HDAC1 and HDAC2 in the progression of neuronal precursors to mature neurons in vivo.cerebellum ͉ hippocampus ͉ neurogenesis ͉ neuronal precursors H istone acetyltransferases (HATs) and histone deacetylases (HDACs) provide the enzymatic basis for transcriptional activation and repression, respectively, through alterations of the chromatin landscape (1). Transcription factors recruit HDACs, either individually, or in repressive complexes to deacetylate lysine residues on histone tails, resulting in chromatin condensation and repression of gene expression (2). There are 4 classes of HDACs that coordinate proper gene regulation for numerous cellular processes: class I (HDAC1, -2, -3, and -8), class II (HDAC4, -5, -6, -7, -9, and -10), sirtuin class III, and class IV (HDAC11) (3). Although much has been learned through in vitro and inhibitor studies, little is known about the biological function of these individual enzymes in vivo (4). We have shown that the class I HDACs, HDAC1 and HDAC2, redundantly regulate cardiac growth and morphogenesis (5), however, the functions of HDAC1 and HDAC2 in other tissues remain unknown.HDAC inhibitors have shown significant potential for therapeutic use in a variety of disorders, including those of the central nervous system (CNS), such as neurodegenerative disease, motor neuron disease, and a number of other neurological disease states (6). Furthermore, it has been shown that HDAC inhibitors induce differentiation of both embryonic and adult cortical neuronal progenitor cells to neurons specifically (7-9). The wide expression pattern of a number of HDACs in the developing brain suggests specific roles for individual HDACs in neuronal development (10), however, the broad inhibition of classical HDAC inhibitors has precluded the analysis of individual HDACs pharmacologically. Additionally, the early lethality associated with global deletion of class I HDACs in knockout mice has compounded the difficulties in analyzing the functions of these enzymes during specific stages of neurogenesis in vivo (5, 11).To further investigate the specific roles of HDAC1 and HDAC2 in neuronal development, we generated conditional deletions of HDAC1 and HDAC2 in the central nervous system. Here, we show both HDAC1 and HDAC2 are required for multip...

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mentioning

confidence: 99%

Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Montgomery¹,

Hsieh²,

Barbosa³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

275

247

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“…It has been shown that activation of neuronal gene expression is achieved by the removal of multi-protein complexes containing co-repressors, HDACs and repressor element 1 (RE1)-silencing transcription factor (REST) from the promoters of differentiation-asociated genes (Roopra et al, 2000;Ballas et al, 2005). In agreement with these findings, treating cells with HDAC inhibitors (Kondo, 2006;Balasubramaniyan et al, 2006;Lyssiotis et al, 2007;Siebzehnrubl et al, 2007), and systemic administration of HDAC inhibitors to either neonatal or adult animals increases neuronal gene expression and favors neurogenesis. More recently, it has also been suggested that the assembly of specific SWI/SNF complexes participates in defining the timing of neurogenesis (Lessard et al, 2007).…”

Section: Timing Of Differentiation Caused By Disinhibition Of Late DImentioning

confidence: 83%

Events at the transition between cell cycle exit and oligodendrocyte progenitor differentiation: the role of HDAC and YY1

Sandoval

Casaccia‐Bonnefil

2007

Neuron Glia Biol.

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The complexity of the adult brain is the result of an integrated series of developmental events that depends on appropriate timing of differentiation. The importance of transcriptional regulatory networks and epigenetic mechanisms of regulation of gene expression is becoming increasingly evident. Among these mechanisms, previous work has revealed the importance of histone deacetylation in oligodendrocyte differentiation. In this manuscript we define the region of interaction between transcription factor Yin-Yang 1 (YY1) and histone deacetylase 1, and characterize the functional consequences of YY1 overexpression on the differentiation of oligodendrocyte progenitors.

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“…Whether new neurons, from either endogenous or exogenous sources, survive long enough to contribute to recovery of function remains unclear. However, it is very clear that epigenetic re-programming of cells occurs at different stages of life, and that HDAC inhibitors can drive both endogenous and isolated embryonic and adult neural progenitor cells to differentiate into neurons [54][55][56][57].…”

Section: "Neuronogenesis" After Ischemic Injurymentioning

confidence: 99%

Novel Protective Effects of Histone Deacetylase Inhibition on Stroke and White Matter Ischemic Injury

2013

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Understanding how epigenetics influences the process and progress of a stroke could yield new targets and therapeutics for use in the clinic. Experimental evidence suggests that inhibitors of zinc-dependent histone deacetylases can protect neurons, axons, and associated glia from the devastating effects of oxygen and glucose deprivation. While the specific enzymes involved have yet to be clearly identified, there are hints from somewhat selective chemical inhibitors and also from the use of specific small hairpin RNAs to transiently knockdown protein expression. Neuroprotective mechanisms implicated thus far include the upregulation of extracellular glutamate clearance, inhibition of p53-mediated cell death, and maintenance of mitochondrial integrity. The histone deacetylases have distinct cellular and subcellular localizations, and discrete substrates. As a number of chemical inhibitors are already in clinical use for the treatment of cancer, repurposing for the stroke clinic should be expedited.

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Effects of histone deacetylation inhibition on neuronal differentiation of embryonic mouse neural stem cells

Cited by 124 publications

References 42 publications

Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Events at the transition between cell cycle exit and oligodendrocyte progenitor differentiation: the role of HDAC and YY1

Novel Protective Effects of Histone Deacetylase Inhibition on Stroke and White Matter Ischemic Injury

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