Редактирование: HDAC2

Histone deacetylase 2 (EC 3.5.1.98) (HD2)

==Publications==

{{medline-entry
|title=EEF1A1 deacetylation enables transcriptional activation of remyelination.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32647127
|abstract=Remyelination of the peripheral and central nervous systems (PNS and CNS, respectively) is a prerequisite for functional recovery after lesion. However, this process is not always optimal and becomes inefficient in the course of multiple sclerosis. Here we show that, when acetylated, eukaryotic elongation factor 1A1 (eEF1A1) negatively regulates PNS and CNS remyelination. Acetylated eEF1A1 (Ac-eEF1A1) translocates into the nucleus of myelinating cells where it binds to Sox10, a key transcription factor for PNS and CNS myelination and remyelination, to drag Sox10 out of the nucleus. We show that the lysine acetyltransferase Tip60 acetylates eEF1A1, whereas the histone deacetylase [[HDAC2]] deacetylates eEF1A1. Promoting eEF1A1 deacetylation maintains the activation of Sox10 target genes and increases PNS and CNS remyelination efficiency. Taken together, these data identify a major mechanism of Sox10 regulation, which appears promising for future translational studies on PNS and CNS remyelination.
|mesh-terms=* Acetylation
* Aging
* Animals
* Cell Dedifferentiation
* Cell Nucleus
* Histone Deacetylase 1
* Histone Deacetylase 2
* Lysine Acetyltransferase 5
* Mice
* Models, Biological
* Oligodendroglia
* Peptide Elongation Factor 1
* Peripheral Nervous System
* Recovery of Function
* Remyelination
* SOXE Transcription Factors
* STAT3 Transcription Factor
* Schwann Cells
* Theophylline
* Trans-Activators
* Transcriptional Activation

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347577
}}
{{medline-entry
|title=Endothelial toll-like receptor 4 maintains lung integrity via epigenetic suppression of p16 .
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30790400
|abstract=We previously reported that the canonical innate immune receptor toll-like receptor 4 ([[TLR4]]) is critical in maintaining lung integrity. However, the molecular mechanisms via which [[TLR4]] mediates its effect remained unclear. In the present study, we identified distinct contributions of lung endothelial cells (Ec) and epithelial cells [[TLR4]] to pulmonary homeostasis using genetic-specific, lung- and cell-targeted in vivo methods. Emphysema was significantly prevented via the reconstituting of human [[TLR4]] expression in the lung Ec of [[TLR4]]-/- mice. Lung Ec-silencing of [[TLR4]] in wild-type mice induced emphysema, highlighting the specific and distinct role of Ec-expressed [[TLR4]] in maintaining lung integrity. We also identified a previously unrecognized role of [[TLR4]] in preventing expression of p16  , a senescence-associated gene. Lung Ec-p16  -silencing prevented [[TLR4]]-/- induced emphysema, revealing a new functional role for p16  in lungs. [[TLR4]] suppressed endogenous p16  expression via [[HDAC2]]-mediated deacetylation of histone H4. These findings suggest a novel role for [[TLR4]] in maintaining of lung homeostasis via epigenetic regulation of senescence-related gene expression.
|mesh-terms=* Animals
* Cells, Cultured
* Cyclin-Dependent Kinase Inhibitor p16
* Endothelial Cells
* Epigenesis, Genetic
* Humans
* Lung
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Mice, Transgenic
* Toll-Like Receptor 4
|keywords=* HDAC2
* aging
* cellular senescence
* emphysema
* p16INK4a
* toll-like receptor 4
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516428
}}
{{medline-entry
|title=Budesonide, Aclidinium and Formoterol in combination limit inflammaging processes in bronchial epithelial cells exposed to cigarette smoke.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30659954
|abstract=Inflammation and cellular senescence (also called inflammaging) are involved in the pathogenesis of premature lung aging, a key driver of chronic obstructive pulmonary disease (COPD). Downregulation of histone deacetylases and FoxO3 expression, activation of the ERK 1/2 pathway and IL-8 increase are hallmarks of lung inflammaging. The effects of Budesonide (BUD), Aclidinium (ACL) and Formoterol (FO) on lung inflammaging are unknown. This study was aimed to assess the effects of BUD, ACL and FO in bronchial epithelial cells exposed to cigarette smoke extract (CSE) by evaluating: a) Expression of [[TLR4]] and survivin and LPS binding by flow cytometry; b) expression of [[HDAC2]], [[HDAC3]], [[SIRT1]] and FoxO3 and activation of the ERK 1/2 pathway by western blot; c) IL-8 mRNA levels and release by Real Time-PCR and ELISA, respectively. Reported results show that CSE increased [[TLR4]] and survivin, LPS binding, ERK 1/2 activation, IL-8 release and mRNA levels but decreased [[SIRT1]], [[HDAC2]], [[HDAC3]] and FoxO3 nuclear expression. Combined therapy with BUD, ACL and FO counteracted the effects of CSE on LPS binding, FoxO3 nuclear expression, ERK 1/2 activation, survivin and IL-8 release and mRNA levels. These findings suggest a new role of combination therapy with BUD, ACL and FO in counteracting inflammaging processes induced by cigarette smoke exposure.
|mesh-terms=* Bronchi
* Budesonide
* Cells, Cultured
* Cellular Senescence
* Epithelial Cells
* Extracellular Signal-Regulated MAP Kinases
* Forkhead Box Protein O3
* Formoterol Fumarate
* Humans
* Inflammation
* Lipopolysaccharides
* Sirtuin 1
* Smoke
* Tobacco
* Toll-Like Receptor 4
* Tropanes
|keywords=* Bronchial epithelial cells
* Cell senescence
* Cigarette smoke
* Inflammaging
* Inhalatory drugs
|full-text-url=https://sci-hub.do/10.1016/j.exger.2019.01.016
}}
{{medline-entry
|title=[[HDAC3]] Regulates the Transition to the Homeostatic Myelinating Schwann Cell State.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30517863
|abstract=The formation of myelinating Schwann cells (mSCs) involves the remarkable biogenic process, which rapidly generates the myelin sheath. Once formed, the mSC transitions to a stable homeostatic state, with loss of this stability associated with neuropathies. The histone deacetylases histone deacetylase 1 (HDAC1) and [[HDAC2]] are required for the myelination transcriptional program. Here, we show a distinct role for [[HDAC3]], in that, while dispensable for the formation of mSCs, it is essential for the stability of the myelin sheath once formed-with loss resulting in progressive severe neuropathy in adulthood. This is associated with the prior failure to downregulate the biogenic program upon entering the homeostatic state leading to hypertrophy and hypermyelination of the mSCs, progressing to the development of severe myelination defects. Our results highlight distinct roles of HDAC1/2 and [[HDAC3]] in controlling the differentiation and homeostatic states of a cell with broad implications for the understanding of this important cell-state transition.
|mesh-terms=* Aging
* Animals
* Histone Deacetylases
* Homeostasis
* Mice, Inbred C57BL
* Myelin Sheath
* Rats
* Schwann Cells
* Sciatic Nerve
* Transcription, Genetic
|keywords=* HDACs
* Schwann cells
* biogenesis
* homeostasis
* neuropathy
* peripheral nerve
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293966
}}
{{medline-entry
|title=Altered modulation of lamin A/C-[[HDAC2]] interaction and p21 expression during oxidative stress response in HGPS.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30109767
|abstract=Defects in stress response are main determinants of cellular senescence and organism aging. In fibroblasts from patients affected by Hutchinson-Gilford progeria, a severe [[LMNA]]-linked syndrome associated with bone resorption, cardiovascular disorders, and premature aging, we found altered modulation of [[CDKN1A]], encoding p21, upon oxidative stress induction, and accumulation of senescence markers during stress recovery. In this context, we unraveled a dynamic interaction of lamin A/C with [[HDAC2]], an histone deacetylase that regulates [[CDKN1A]] expression. In control skin fibroblasts, lamin A/C is part of a protein complex including [[HDAC2]] and its histone substrates; protein interaction is reduced at the onset of DNA damage response and recovered after completion of DNA repair. This interplay parallels modulation of p21 expression and global histone acetylation, and it is disrupted by [[LMNA]]mutations leading to progeroid phenotypes. In fact, HGPS cells show impaired lamin A/C-[[HDAC2]] interplay and accumulation of p21 upon stress recovery. Collectively, these results link altered physical interaction between lamin A/C and [[HDAC2]] to cellular and organism aging. The lamin A/C-[[HDAC2]] complex may be a novel therapeutic target to slow down progression of progeria symptoms.
|mesh-terms=* Adolescent
* Aged
* Cells, Cultured
* Child
* Child, Preschool
* Cyclin-Dependent Kinase Inhibitor p21
* DNA Damage
* DNA Repair
* Female
* Fibroblasts
* Gene Expression Regulation
* Histone Deacetylase 2
* Humans
* Lamin Type A
* Male
* Mutation
* Oxidative Stress
* Progeria
* Protein Binding
* Substrate Specificity
|keywords=* CDKN1A (p21WAF1/Cip1)
* Hutchinson-Gilford progeria syndrome (HGPS)
* aging
* histone deacetylase 2 (HDAC2)
* lamin A/C
* oxidative stress
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156291
}}
{{medline-entry
|title=Histone deacetylase 1 expression is inversely correlated with age in the short-lived fish Nothobranchius furzeri.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29951776
|abstract=Aging is associated with profound changes in the epigenome, resulting in alterations of gene expression, epigenetic landscape, and genome architecture. Class I Histone deacetylases (HDACs), consisting of [[HDAC1]], [[HDAC2]], [[HDAC3]], and [[HDAC8]], play a major role in epigenetic regulation of chromatin structure and transcriptional control, and have been implicated as key players in the pathogenesis of age-dependent diseases and disorders affecting health and longevity. Here, we report the identification of class I Hdac orthologs and their detailed spatio-temporal expression profile in the short-lived fish Nothobranchius furzeri from the onset of embryogenesis until old age covering the entire lifespan of the organism. Database search of the recently annotated N. furzeri genomes retrieved four distinct genes: two copies of hdac1 and one copy of each hdac3 and hdac8. However, no hdac2 ortholog could be identified. Phylogenetic analysis grouped the individual killifish class I Hdacs within the well-defined terminal clades. We find that upon aging, Hdac1 is significantly down-regulated in muscle, liver, and brain, and this age-dependent down-regulation in brain clearly correlates with increased mRNA levels of the cyclin-dependent kinase inhibitor cdkn1a (p21). Furthermore, this apparent reduction of class I HDACs in transcript and protein levels is mirrored in the mouse brain, highlighting an evolutionarily conserved role of class I HDACs during normal development and in the aging process.
|mesh-terms=* Aging
* Animals
* Fishes
* Gene Expression Profiling
* Histone Deacetylase 1
* Immunohistochemistry
* Mice
* Mice, Inbred C57BL
* Survival Analysis
|keywords=* Aging
* Epigenetics
* Histone deacetylase
* Nothobranchius furzeri
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096771
}}
{{medline-entry
|title=Histone Deacetylase 2 Inhibition Attenuates Downregulation of Hippocampal Plasticity Gene Expression during Aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28364391
|abstract=The brain undergoes several anatomical, biochemical, and molecular changes during aging, which subsequently result in downregulation of synaptic plasticity genes and decline of memory. However, the regulation of these genes during aging is not clearly understood. Previously, we reported that the expression of histone deacetylase (HDAC)2 was upregulated in the hippocampus of old mice and negatively correlated with the decline in recognition memory. As [[HDAC2]] regulates key synaptic plasticity neuronal immediate early genes (IEGs), we have examined their expression and epigenetic regulation. We noted that the expression of neuronal IEGs decreased both at mRNA and protein level in the hippocampus of old mice. To explore the underlying regulation, we analyzed the binding of [[HDAC2]] and level of histone acetylation at the promoter of neuronal IEGs. While the binding of [[HDAC2]] was higher, H3K9 and H3K14 acetylation level was lower at the promoter of these genes in old as compared to young and adult mice. Further, we inhibited [[HDAC2]] non-specifically by sodium butyrate and specifically by antisense oligonucleotide to recover epigenetic modification, expression of neuronal IEGs, and memory in old mice. Inhibition of [[HDAC2]] increased histone H3K9 and H3K14 acetylation level at the promoter of neuronal IEGs, their expression, and recognition memory in old mice as compared to control. Thus, inhibition of [[HDAC2]] can be used as a therapeutic target to recover decline in memory due to aging and associated neurological disorders.
|mesh-terms=* Aging
* Animals
* Down-Regulation
* Epigenesis, Genetic
* Gene Expression
* Hippocampus
* Histone Deacetylase 2
* Histone Deacetylase Inhibitors
* Male
* Memory
* Mice
* Neuronal Plasticity
|keywords=* HDAC inhibitor
* HDAC2
* Histone acetylation
* Memory
* Neuronal IEG
|full-text-url=https://sci-hub.do/10.1007/s12035-017-0490-x
}}
{{medline-entry
|title=Non-sirtuin histone deacetylases in the control of cardiac aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25791169
|abstract=Histone deacetylases (HDACs) catalyze the removal of acetyl-groups from lysine residues within nucelosomal histone tails and thousands of non-histone proteins. The 18 mammalian HDACs are grouped into four classes. Classes I, II and IV HDACs employ zinc as a co-factor for catalytic activity, while class III HDACs (also known as sirtuins) require NAD  for enzymatic function. Small molecule inhibitors of zinc-dependent HDACs are efficacious in multiple pre-clinical models of pressure overload and ischemic cardiomyopathy, reducing pathological hypertrophy and fibrosis, and improving contractile function. Emerging data have revealed numerous mechanisms by which HDAC inhibitors benefit the heart, including suppression of oxidative stress and inflammation, inhibition of MAP kinase signaling, and enhancement of cardiac protein aggregate clearance and autophagic flux. Here, we summarize recent findings with zinc-dependent HDACs and HDAC inhibitors in the heart, focusing on newly described functions for distinct HDAC isoforms (e.g. [[HDAC2]], [[HDAC3]] and HDAC6). Potential for pharmacological HDAC inhibition as a means of treating age-related cardiac dysfunction is also discussed. This article is part of a Special Issue entitled: CV Aging. 
|mesh-terms=* Aging
* Animals
* Cardiomegaly
* Heart Failure
* Histone Deacetylase Inhibitors
* Histone Deacetylases
* Histones
* Humans
* Inflammation
* Isoenzymes
* Myocardium
* Oxidative Stress
* Protein Processing, Post-Translational
* Signal Transduction
|keywords=* Aging
* Heart failure
* Histone deacetylase
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459895
}}
{{medline-entry
|title=Histone deacetylase 2 in the mouse hippocampus: attenuation of age-related increase by caloric restriction.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24093534
|abstract=The aging process in the hippocampus is associated with aberrant epigenetic marks, such as DNA methylation and histone tail alterations. Recent evidence suggests that caloric restriction (CR) can potentially delay the aging process, while upregulation of antioxidants may also have a beneficial effect in this respect. We have recently observed that CR attenuates age-related changes in the levels of the epigenetic molecules DNA methyltransferase 3a, 5-methylcytidine (5- mC) and 5-hydroxymethylcytosine in the mouse hippocampus while overexpression of the antioxidant Cu/Zn superoxide dismutase 1 ([[SOD1]]) does not. However, the impact of aging on the levels of histone-modifying enzymes such as histone deacetylase 2 ([[HDAC2]]) in the hippocampus has not been studied in much detail. Here, we investigated immunoreactivity (IR) of [[HDAC2]] in three subregions of the hippocampus (dentate gyrus, [[CA3]] and [[CA1]]-2) of mice taken from large cohorts of aging wild-type and transgenic mice overexpressing normal human [[SOD1]], which were kept under normal diet or CR from weaning onwards. Independent from the genotype, aging (between 12 and 24 months) increased levels of [[HDAC2]] IR in the hippocampus. Moreover, CR prevented this age-related increase, particularly in the [[CA3]] and [[CA1]]-2 subregions, while [[SOD1]] overexpression did not. Quantitative image analyses showed that [[HDAC2]] IR correlated positively with 5-mC IR while these markers were shown to colocalize in the nucleus of hippocampal cells. Together with recent literature reports, these findings suggest that altered levels of epigenetic regulatory proteins including [[HDAC2]] regulate age-related changes in the mouse hippocampus and that CR may prevent these age-related changes. 
|mesh-terms=* Aging
* Animals
* Caloric Restriction
* Hippocampus
* Histone Deacetylase 2
* Male
* Mice

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966721
}}