Histone H3K4me1 and H3K27ac play roles in nucleosome eviction and eRNA transcription, respectively, at enhancers

Kang, Young-Seok; Kim, Yea Woon; Kang, Jin Gu; Kim, AeRi

doi:10.1096/fj.202100488r

Cited by 43 publications

(29 citation statements)

References 58 publications

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“…The key enzymes of histone acetylation, KATs, directly acetylate several key transcription factors such as p53, FOXO1, and C/EBPα to modulate the transcription activity and affect cell homeostasis [ 300 , 384 , 385 , 386 ]. Besides ES, epigenetics also plays important roles in somatic stem cells, and HDACs, especially HDAC1 and HDAC2 expression levels, decrease significantly upon tissue differentiation, while HDAC3 and DNMT1 keep the same expression [ 387 , 388 , 389 ].…”

Section: Epigenetics In Normal Development and Tumorigenesismentioning

confidence: 99%

An Epigenetic Role of Mitochondria in Cancer

Liu

Chen

Wang

et al. 2022

Cells

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Mitochondria are not only the main energy supplier but are also the cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD+, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which are the main substrates for DNA methylation and histone post-translation modifications, essential for gene transcriptional regulation and cell fate determination. Tumorigenesis is attributed to many factors, including gene mutations and tumor microenvironment. Mitochondria and epigenetics play essential roles in tumor initiation, evolution, metastasis, and recurrence. Targeting mitochondrial metabolism and epigenetics are promising therapeutic strategies for tumor treatment. In this review, we summarize the roles of mitochondria in key metabolites required for epigenetics modification and in cell fate regulation and discuss the current strategy in cancer therapies via targeting epigenetic modifiers and related enzymes in metabolic regulation. This review is an important contribution to the understanding of the current metabolic-epigenetic-tumorigenesis concept.

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Section: Epigenetics In Normal Development and Tumorigenesismentioning

confidence: 99%

An Epigenetic Role of Mitochondria in Cancer

Liu

Chen

Wang

et al. 2022

Cells

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“…In addition, the SangerBox data showed a significant correlation between CCT3 and the methyltransferases ( Supplementary Figure S8C ). Histone H3K27ac modification is necessary for enhancer to activate the transcription of target genes ( Kang et al, 2021 ). We found a strong H3K27ac signal in CCT3 promoter region by the WashU database in various tumor cells ( Figure 12A ).…”

Section: Resultsmentioning

confidence: 99%

Insights into the roles and driving forces of CCT3 in human tumors

Song²,

Liu³

et al. 2022

Front. Pharmacol.

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CCT3 played a key role in many cancers. This study aimed to further explore the characteristics of CCT3 from a pan-cancer perspective and reveal the driving forces for CCT3. By bioinformatic analysis, we found that the mRNA and protein levels of CCT3 were abnormally elevated in most tumor types and were correlated with poor prognosis. Single-cell sequencing data indicated an abnormal increase of CCT3 expression in both malignant cells and multiple immune cells. In the tumor microenvironment, CCT3 expression was negatively relevant with immune cell infiltration and immune checkpoint genes expression. In colon cancer, knockdown of CCT3 inhibited cell proliferation. Gene set enrichment analysis showed that CCT3 may be oncogenic by regulating amino acid metabolism. Furthermore, we predicted sensitive drugs for CCT3 by virtual screening and sensitivity analysis. Many driver genes such as TP53 and KRAS were essential for CCT3 overexpression. Epigenetic factors, enhancers in particular, were also critical for CCT3 expression. Additionally, we constructed the lncRNA/circRNA-miRNA-CCT3 regulatory network. Collectively, CCT3 had the potential to be a diagnostic and prognostic biomarker for multiple tumor types. CCT3 expression was relevant with an immunosuppressive tumor microenvironment. CCT3 could be a new molecular target for colon cancer. Both genetic and epigenetic factors were responsible for CCT3 expression in tumors.

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“…H3K4me1 is found at enhancers and precedes acetylation of H3K27 (Calo and Wysocka 2013 ). These chromatin marks support enhancer–promoter interactions and transcription of enhancer RNAs (Creyghton et al 2010 ; Kang et al 2021 ). H3K4me1 promotes interactions between the enhancers and gene promoters by facilitating the binding of chromatin remodelers (Local et al 2018 ; Yan et al 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Histone 3 lysine 4 monomethylation supports activation of transcription in S. cerevisiae during nutrient stress

et al. 2022

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Mono-methylation of the fourth lysine on the N-terminal tail of histone H3 was found to support the induction of RNA polymerase II transcription in S. cerevisiae during nutrient stress. In S. cerevisiae, the mono-, di- and tri-methylation of lysine 4 on histone H3 (H3K4) is catalyzed by the protein methyltransferase, Set1. The three distinct methyl marks on H3K4 act in discrete ways to regulate transcription. Nucleosomes enriched with tri-methylated H3K4 are usually associated with active transcription whereas di-methylated H3K4 is associated with gene repression. Mono-methylated H3K4 has been shown to repress gene expression in S. cerevisiae and is detected at enhancers and promoters in eukaryotes. S. cerevisiae set1Δ mutants unable to methylate H3K4 exhibit growth defects during histidine starvation. The growth defects are rescued by either a wild-type allele of SET1 or partial-function alleles of set1, including a mutant that predominantly generates H3K4me1 and not H3K4me3. Rescue of the growth defect is associated with induction of the HIS3 gene. Growth defects observed when set1Δ cultures were starved for isoleucine and valine were also rescued by wild-type SET1 or partial-function set1 alleles. The results show that H3K4me1, in the absence of H3K4me3, supports transcription of the HIS3 gene and expression of one or more of the genes required for biosynthesis of isoleucine and valine during nutrient stress. Set1-like methyltransferases are evolutionarily conserved, and research has linked their functions to developmental gene regulation and several cancers in higher eukaryotes. Identification of mechanisms of H3K4me1-mediated activation of transcription in budding yeast will provide insight into gene regulation in all eukaryotes.

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Histone H3K4me1 and H3K27ac play roles in nucleosome eviction and eRNA transcription, respectively, at enhancers

Cited by 43 publications

References 58 publications

An Epigenetic Role of Mitochondria in Cancer

An Epigenetic Role of Mitochondria in Cancer

Insights into the roles and driving forces of CCT3 in human tumors

Histone 3 lysine 4 monomethylation supports activation of transcription in S. cerevisiae during nutrient stress

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