Expression of hMOF, but not HDAC4, is responsible for the global histone H4K16 acetylation in gastric carcinoma

Zhu, Lin; Yang, Jiaxing; Zhao, Lifeng; Yu, Xue; Wang, Lingyao; Wang, Fei; Cai, Yong; Jin, Jingji

doi:10.3892/ijo.2015.2956

Cited by 30 publications

(17 citation statements)

References 29 publications

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“…Accordingly, a number of more recent studies have established that the KAT responsible for H4K16ac, MOF, is expressed at low levels in a range of cancers, including breast 170 , ovarian 171 , colorectal 172 , renal 172 , gastric 172,173 and hepatocellular cancers 174 . Similar to H4K16ac, low MOF levels correlate with poor prognosis and increased metastasis [170][171][172][173][174] . The significance of low H4K16ac and MOF levels in cancer remains to be determined as, counterintuitively, MOF is required for cell proliferation in mammalian cell culture systems 31 .…”

Section: Diencephalonmentioning

confidence: 99%

The many lives of KATs — detectors, integrators and modulators of the cellular environment

2018

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Research over the past three decades has firmly established lysine acetyltransferases (KATs) as central players in regulating transcription. Recent advances in genomic sequencing, metabolomics, animal models and mass spectrometry technologies have uncovered unexpected new roles for KATs at the nexus between the environment and transcriptional regulation. Thousands of reversible acetylation sites have been mapped in the proteome that respond dynamically to the cellular milieu and maintain major processes such as metabolism, autophagy and stress response. Concurrently , researchers are continuously uncovering how deregulation of KAT activity drives disease, including cancer and developmental syndromes characterized by severe intellectual disability. These novel findings are reshaping our view of KATs away from mere modulators of chromatin to detectors of the cellular environment and integrators of diverse signalling pathways with the ability to modify cellular phenotype.

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Section: Diencephalonmentioning

confidence: 99%

The many lives of KATs — detectors, integrators and modulators of the cellular environment

2018

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“…Reduced H4K16ac is strongly associated with a wide range of malignancies . Consistently, independent studies have reported MOF to be downregulated in a panel of cancer types including breast cancer , ovarian epithelial cancer , colorectal carcinoma , gastric cancer , hepatocellular carcinoma , and medulloblastoma . How the downregulation of MOF and H4K16ac drives tumorigenesis remains unknown, as paradoxically, depletion of MOF leads to cell cycle arrest in primary cell culture systems .…”

Section: Nsl Complex In Human Health and Diseasementioning

confidence: 87%

The non‐specific lethal ( NSL ) complex at the crossroads of transcriptional control and cellular homeostasis

2019

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The functionality of chromatin is tightly regulated by post‐translational modifications that modulate transcriptional output from target loci. Among the post‐translational modifications of chromatin, reversible ε‐lysine acetylation of histone proteins is prominent at transcriptionally active genes. Lysine acetylation is catalyzed by lysine acetyltransferases (KATs), which utilize the central cellular metabolite acetyl‐CoA as their substrate. Among the KATs that mediate lysine acetylation, males absent on the first (MOF/KAT8) is particularly notable for its ability to acetylate histone 4 lysine 16 (H4K16ac), a modification that decompacts chromatin structure. MOF and its non‐specific lethal (NSL) complex members have been shown to localize to gene promoters and enhancers in the nucleus, as well as to microtubules and mitochondria to regulate key cellular processes. Highlighting their importance, mutations or deregulation of NSL complex members has been reported in both human neurodevelopmental disorders and cancer. Based on insight gained from studies in human, mouse, and Drosophila model systems, this review discusses the role of NSL‐mediated lysine acetylation in a myriad of cellular functions in both health and disease. Through these studies, the importance of the NSL complex in regulating core transcriptional and signaling networks required for normal development and cellular homeostasis is beginning to emerge.

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“…Our results, by showing higher hMOF protein and H4K16ac levels in HCC with mVI, suggest a transcription activation of key genes involved in cell invasion in these tumours. On the other hand, several studies have shown that hMOF was downregulated in various tumours, such as gastric cancer, breast cancer and medulloblastoma vs the non‐tumour counterpart. Altogether, these findings suggest that hMOF may play various roles depending on the tumour type.…”

Section: Discussionmentioning

confidence: 99%

The histone acetyltransferase hMOF promotes vascular invasion in hepatocellular carcinoma

Poté

Cros

Laouirem

et al. 2020

Liver International

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Background & Aims Vascular invasion is a major prognostic factor in hepatocellular carcinoma (HCC). We previously identified histone H4 acetylated at lysine 16 (H4K16ac), a histone modification involved in transcription activation, as a biomarker of microvascular invasion (mVI) in HCC. This study aimed to investigate the role of hMOF, the histone acetyltransferase responsible for H4K16 acetylation, in the process of vascular invasion in HCC. Methods hMOF expression was assessed by RT‐qPCR and immunohistochemistry in a retrospective series of HCC surgical samples, and correlated with the presence of mVI. The functional role of hMOF in HCC vascular invasion was investigated in vitro in HCC cell lines using siRNA, transcriptomic analysis and transwell invasion assay, and in vivo using a Zebrafish embryo xenograft model. Results We found that hMOF was significantly upregulated at the protein level in HCC with mVI, compared with HCC without mVI (P < .01). Transcriptomic analysis showed that hMOF downregulation in HCC cell line lead to significant downregulation of key genes and pathways involved in vascular invasion. These results were confirmed by transwell invasion assay, where hMOF downregulation significantly reduced HCC cells invasion. Finally, hMOF downregulation significantly reduced tumour cell intravasation and metastasis in vivo. Conclusions Altogether, these results underpin a critical role for hMOF in vascular invasion in HCC, via transcription activation of key genes involved in this process. These data confirm the major role of epigenetic alterations in HCC progression, and pave the way for future therapies targeting hMOF in HCC.

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Expression of hMOF, but not HDAC4, is responsible for the global histone H4K16 acetylation in gastric carcinoma

Cited by 30 publications

References 29 publications

The many lives of KATs — detectors, integrators and modulators of the cellular environment

The many lives of KATs — detectors, integrators and modulators of the cellular environment

The non‐specific lethal ( NSL ) complex at the crossroads of transcriptional control and cellular homeostasis

The histone acetyltransferase hMOF promotes vascular invasion in hepatocellular carcinoma

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