Histone Deacetylase 3 Is Necessary for Proper Brain Development

Norwood, Jordan N; Franklin, Jade M.; Sharma, Dharmendra; D’Mello, Santosh R.

doi:10.1074/jbc.m114.576397

Cited by 62 publications

(82 citation statements)

References 24 publications

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“…While class I HDACs have been shown to be involved in neural stem/progenitor cell development (Jiang and Hsieh, 2014; Montgomery et al, 2009; Norwood et al, 2014), the present study reveals a distinct role of Hdac3 in glial subtype switching, and in establishment and maintenance of OL identity. This fate switch mechanism is unique to Hdac3, as knockouts of Hdac1, Hdac2, or both together, or Hdac8, do not alter OPC fate or induce astrogliogenesis.…”

Section: Discussionmentioning

confidence: 57%

Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch

Zhang

Liu

et al. 2016

Developmental Cell

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Summary Establishment and maintenance of CNS glial cell identity ensures proper brain development and function, yet the epigenetic mechanisms underlying glial fate control remain poorly understood. Here we show that the histone deacetylase Hdac3 controls oligodendrocyte-specification gene Olig2 expression, and functions as a molecular switch for oligodendrocyte and astrocyte lineage determination. Hdac3 ablation leads to a significant increase of astrocytes with a concomitant loss of oligodendrocytes. Lineage-tracing indicates that the ectopic astrocytes originate from oligodendrocyte progenitors. Genome-wide occupancy analysis reveals that Hdac3 interacts with p300 to activate oligodendroglial lineage-specific genes, while suppressing astroglial differentiation genes including NFIA. Furthermore, we find that Hdac3 modulates the acetylation state of Stat3, and competes with Stat3 for p300 binding to antagonize astrogliogenesis. Thus, our data suggest that Hdac3 cooperates with p300 to prime and maintain oligodendrocyte identity while inhibiting NFIA and Stat3-mediated astrogliogenesis, and thereby regulates phenotypic commitment at the point of oligodendrocyte-astrocytic fate decision.

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Section: Discussionmentioning

confidence: 57%

Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch

Zhang

Liu

et al. 2016

Developmental Cell

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“…Further immunohistochemical analysis of the subcellular localization of this truncated HDAC4 protein would be of interest, as analyses of the localization of HDAC4 mutants suggests that this fragment with NLS intact but no NES would accumulate in the nucleus (Sando et al, 2012;Wang & Yang, 2001). The presence of HDAC3 is essential for normal brain development, as cBKO of HDAC3 in neural progenitors with Nestin-Cre results in severe cellular cytoarchitectural abnormalities in neurons and premature death within a day of birth (Norwood, Franklin, Sharma, & D'Mello, 2014). Moreover, focal knockout of HDAC3 via intrahippocampal delivery of an adeno-associated viral vector carrying Cre recombinase to the hippocampus of FLOX-HDAC3 mice correlates with increased histone acetylation (McQuown et al, 2011b).…”

Section: Hdac4 Is Not Required For Brain Developmentmentioning

confidence: 97%

The Class IIa histone deacetylase HDAC4 and neuronal function: Nuclear nuisance and cytoplasmic stalwart?

Fitzsimons

2015

Neurobiology of Learning and Memory

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“…Moreover, HDAC4 may be implicated in neurodevelopment via interacting with HDAC3 which is necessary for brain development (Norwood et al, 2014). In human, both HDAC4 deletion and duplication lead to mental retardation and intelligence disability, suggesting that HDAC4 plays an important role in neurodevelopment which directly links to cognitive function (Shim et al, 2014).…”

Section: Hdac4 In Cognitive Function and Molecular Mechanismsmentioning

confidence: 99%

Aberrant Expression of Histone Deacetylases 4 in Cognitive Disorders: Molecular Mechanisms and a Potential Target

Hou

Wang

et al. 2016

Front. Mol. Neurosci.

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Histone acetylation is a major mechanism of chromatin remodeling, contributing to epigenetic regulation of gene transcription. Histone deacetylases (HDACs) are involved in both physiological and pathological conditions by regulating the status of histone acetylation. Although histone deacetylase 4 (HDAC4), a member of the HDAC family, may lack HDAC activity, it is actively involved in regulating the transcription of genes involved in synaptic plasticity, neuronal survival, and neurodevelopment by interacting with transcription factors, signal transduction molecules and HDAC3, another member of the HDAC family. HDAC4 is highly expressed in brain and its homeostasis is crucial for the maintenance of cognitive function. Accumulated evidence shows that HDAC4 expression is dysregulated in several brain disorders, including neurodegenerative diseases and mental disorders. Moreover, cognitive impairment is a characteristic feature of these diseases. It indicates that aberrant HDAC4 expression plays a pivotal role in cognitive impairment of these disorders. This review aims to describe the current understanding of HDAC4’s role in the maintenance of cognitive function and its dysregulation in neurodegenerative diseases and mental disorders, discuss underlying molecular mechanisms, and provide an outlook into targeting HDAC4 as a potential therapeutic approach to rescue cognitive impairment in these diseases.

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Histone Deacetylase 3 Is Necessary for Proper Brain Development

Cited by 62 publications

References 24 publications

Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch

Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch

The Class IIa histone deacetylase HDAC4 and neuronal function: Nuclear nuisance and cytoplasmic stalwart?

Aberrant Expression of Histone Deacetylases 4 in Cognitive Disorders: Molecular Mechanisms and a Potential Target

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