Erratum: Corrigendum: The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy

Füllgrabe, Jens; Lynch-Day, Melinda A.; Heldring, Nina; Li, Wenbo; Struijk, Robert B.; Ma, Qi; Hermanson, Ola; Rosenfeld, Michael G.; Klionsky, Daniel J.; Joseph, Bertrand

doi:10.1038/nature22027

Cited by 5 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Having established that KANSL1-deficiency results in increased oxidative stress causing elevated autophagosome formation and reduced synaptic activity, we wondered what causes the autophagosome accumulation in KANSL1-deficient cells. Increased autophagic flux is known to induce a regulatory feedback-loop in which induction of autophagy is coupled to a reduction in H4K16ac through downregulation of hMOF in MEF cells [15]. However, we did not find a reduction in H4K16ac in KANSL1-deficient cells at the basal level.…”

Section: Impaired Feedback-loop and Decreased Lysosomal Activity In Kdvs Cellscontrasting

confidence: 86%

“…Gene ontology analysis identified changed promoter activation of genes within oxidoreductase and mitochondria pathways [22], suggesting increased oxidative stress in KdVS mice. We performed qPCRs for a set of H4K16ac regulated ATG genes [15], that showed differentially activated promoters in the KdVS mouse model. We identified SOD1 (superoxide dismutase 1), an antioxidant enzyme that reduces superoxide, to be about one third lower expressed in KdVS patient derived iPSCs (Figure S2A).…”

Section: Autophagosome Accumulation Is Caused By Increased Oxidative Stressmentioning

confidence: 99%

“…Similarly, H3K27me3 represses transcription of several negative regulators of MTOR, ensuring high MTOR activity in order to suppress autophagy [14]. Furthermore, ATG gene expression is regulated by the acetylation of histone H4 at lysine residue 16 (H4K16ac), which is mediated by the acetyltransferase KAT8/ hMOF/MYST1 [15]. While H4K16ac generally ensures active ATG gene expression, autophagy induction is followed by a reduction in H4K16ac and decreased ATG gene expression [15].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, ATG gene expression is regulated by the acetylation of histone H4 at lysine residue 16 (H4K16ac), which is mediated by the acetyltransferase KAT8/ hMOF/MYST1 [15]. While H4K16ac generally ensures active ATG gene expression, autophagy induction is followed by a reduction in H4K16ac and decreased ATG gene expression [15]. This negative feedback-loop prevents prolonged autophagy and subsequent cell death, indicating how essential balanced autophagy is for cell survival, but also function.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders

et al. 2021

View full text Add to dashboard Cite

Macroautophagy (hereafter referred to as autophagy) is a finely tuned process of programmed degradation and recycling of proteins and cellular components, which is crucial in neuronal function and synaptic integrity. Mounting evidence implicates chromatin remodeling in fine-tuning autophagy pathways. However, this epigenetic regulation is poorly understood in neurons. Here, we investigate the role in autophagy of KANSL1, a member of the nonspecific lethal complex, which acetylates histone H4 on lysine 16 (H4K16ac) to facilitate transcriptional activation. Loss-of-function of KANSL1 is strongly associated with the neurodevelopmental disorder Koolen-de Vries Syndrome (KdVS). Starting from KANSL1-deficient human induced-pluripotent stem cells, both from KdVS patients and genome-edited lines, we identified SOD1 (superoxide dismutase 1), an antioxidant enzyme, to be significantly decreased, leading to a subsequent increase in oxidative stress and autophagosome accumulation. In KANSL1-deficient neurons, autophagosome accumulation at excitatory synapses resulted in reduced synaptic density, reduced GRIA/AMPA receptor-mediated transmission and impaired neuronal network activity. Furthermore, we found that increased oxidative stress-mediated autophagosome accumulation leads to increased MTOR activation and decreased lysosome function, further preventing the clearing of autophagosomes. Finally, by pharmacologically reducing oxidative stress, we could rescue the aberrant autophagosome formation as well as synaptic and neuronal network activity in KANSL1-deficient neurons. Our findings thus point toward an important relation between oxidative stress-induced autophagy and synapse function, and demonstrate the importance of H4K16ac-mediated changes in chromatin structure to balance reactive oxygen species-and MTOR-dependent autophagy.

show abstract

Section: Impaired Feedback-loop and Decreased Lysosomal Activity In Kdvs Cellscontrasting

confidence: 86%

Section: Autophagosome Accumulation Is Caused By Increased Oxidative Stressmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Total expression of caspase 3 changed inapparently, but the p17-caspase 3 was obviously up-regulated. However, studies have shown that MOF also plays an important role in autophagy ( Füllgrabe et al, 2017 ), so further research is needed on the effects of excluding autophagy in apoptotic cells.…”

Section: Discussionmentioning

confidence: 99%

MOF Regulates TNK2 Transcription Expression to Promote Cell Proliferation in Thyroid Cancer

Yang

Chen

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

MOF is a well-known histone acetyltransferase to catalyze acetylation of histone H4 lysine 16 (K16), and it is relevant to diverse biological processes, such as gene transcription, cell cycle, early embryonic development and tumorigenesis. Here, we identify MOF as an oncogene in most thyroid cancer. It is found that expression level of MOF was significantly upregulated in most thyroid cancer tissue samples and cell lines. MOF-deficient in both BHP-10-3 and TT2609 cell lines inhibited cell proliferation by blocking the cell cycle in G1 phase and enhanced cell apoptosis. Mechanistically, MOF bound the TNK2 promoter to activate TNK2 transcription. Furthermore, the expression level of TNK2 was decreased with the histone acetyltransferase inhibitor. Besides, MOF promoted proliferation of thyroid cancer cells through increased phosphorylation of AKT, thus activating the PI3K/AKT pathway. Ultimately, our findings indicated that MOF played an oncogene role in development and progression of thyroid cancer and may be a potential novel target for the treatment of thyroid cancer.

show abstract

Genetic control of autophagy underlies pathogenesis of inflammatory bowel disease

Lassen

Xavier

2017

Mucosal Immunology

View full text Add to dashboard Cite

Autophagy contributes to cellular homeostasis in the face of nutrient deprivation and other cellular stresses. Cell type-specific functions for autophagy are critical in maintaining homeostasis at both the tissue level and at the whole-organism level. Recent work has highlighted the ways in which human genetic variants modulate autophagy to alter epithelial and immune responses in inflammatory bowel disease.

show abstract

Erratum: Corrigendum: The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy

Cited by 5 publications

References 0 publications

Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders

Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders

MOF Regulates TNK2 Transcription Expression to Promote Cell Proliferation in Thyroid Cancer

Genetic control of autophagy underlies pathogenesis of inflammatory bowel disease

Contact Info

Product

Resources

About