SETD6 is a negative regulator of oxidative stress response

Chen, Ayelet; Feldman, Michal; Vershinin, Zlata; Levy, Dan

doi:10.1016/j.bbagrm.2016.01.003

Cited by 28 publications

(21 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FoxM1 methylation by SETD3 adds a new regulatory dimension to this complex process. As many non-histone proteins in the human proteome are known to be methylated2728293031323334, we hypothesize that additional cellular factors that regulate the VEGF signaling under hypoxia may also be methylated by SETD3. Interestingly, two of the known VEGF receptors35, FLT1 (VEGFR1) and KDR (VEGFR2), were identified as SETD3 interacting proteins in our ProtoArray screen (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Chromatin associated SETD3 negatively regulates VEGF expression

Cohn

Feldman

Weil

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

SETD3 is a member of the protein lysine methyltransferase (PKMT) family, which catalyzes the addition of methyl group to lysine residues. Accumulating data suggest that PKMTs are involved in the regulation of a broad spectrum of biological processes by targeting histone and non-histone proteins. Using a proteomic approach, we have identified 172 new SETD3 interacting proteins. We show that SETD3 binds and methylates the transcription factor FoxM1, which has been previously shown to be associated with the regulation of VEGF expression. We further demonstrate that under hypoxic conditions SETD3 is down-regulated. Mechanistically, we find that under basal conditions, SETD3 and FoxM1 are enriched on the VEGF promoter. Dissociation of both SETD3 and FoxM1 from the VEGF promoter under hypoxia correlates with elevated expression of VEGF. Taken together, our data reveal a new SETD3-dependent methylation-based signaling pathway at chromatin that regulates VEGF expression under normoxic and hypoxic conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Chromatin associated SETD3 negatively regulates VEGF expression

Cohn

Feldman

Weil

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…In particular, the absence of HDA-2 may have led to changes on heterochromatin structure by an acetylation unbalance on the promoters of negative regulators of cat-3, including other HDACs. Among negative regulators of the expression of ROS-related genes, histone methylases play a pivotal role (63,64). In N. crassa, the histone methyltransferase DIM-5 and the nonhistone protein heterochromatin protein 1 (HP1) are essential for heterochromatin formation (65).…”

Section: Discussionmentioning

confidence: 99%

Histone Deacetylase HDA-2 Regulates Trichoderma atroviride Growth, Conidiation, Blue Light Perception, and Oxidative Stress Responses

Osorio-Concepción

Cristóbal‐Mondragón

Gutiérrez–Medina

et al. 2017

Appl Environ Microbiol

View full text Add to dashboard Cite

Fungal blue-light photoreceptors have been proposed as integrators of light and oxidative stress. However, additional elements participating in the integrative pathway remain to be identified. In Trichoderma atroviride, the blue-light regulator (BLR) proteins BLR-1 and -2 are known to regulate gene transcription, mycelial growth, and asexual development upon illumination, and recent global transcriptional analysis revealed that the histone deacetylase-encoding gene hda-2 is induced by light. Here, by assessing responses to stimuli in wild-type and Δhda-2 backgrounds, we evaluate the role of HDA-2 in the regulation of genes responsive to light and oxidative stress. Δhda-2 strains present reduced growth, misregulation of the con-1 gene, and absence of conidia in response to light and mechanical injury. We found that the expression of hda-2 is BLR-1 dependent and HDA-2 in turn is essential for the transcription of early and late light-responsive genes that include blr-1, indicating a regulatory feedback loop. When subjected to reactive oxygen species (ROS), Δhda-2 mutants display high sensitivity whereas Δblr strains exhibit the opposite phenotype. Consistently, in the presence of ROS, ROS-related genes show high transcription levels in wild-type and Δblr strains but misregulation in Δhda-2 mutants. Finally, chromatin immunoprecipitations of histone H3 acetylated at Lys9/ Lys14 on cat-3 and gst-1 promoters display low accumulation of H3K9K14ac in Δblr and Δhda-2 strains, suggesting indirect regulation of ROS-related genes by HDA-2. Our results point to a mutual dependence between HDA-2 and BLR proteins and reveal the role of these proteins in an intricate gene regulation landscape in response to blue light and ROS.

show abstract

“…Lysine methylation, catalyzed by protein lysine methyltransferases (PKMTs), is a PTM that plays a key role in a variety of essential cellular signaling pathways (14). In recent years, the PKMT SETD6 has been shown to participate in the NF-κB cascade (15,16), the nuclear factor erythroid 2-related factor 2 (NRF2) oxidative stress response (17), the Wnt signaling pathway (18), nuclear hormone receptor signaling (19), and embryonic stem cell differentiation (20), all of which are vital cellular processes.…”

mentioning

confidence: 99%

The methyltransferase SETD6 regulates Mitotic progression through PLK1 methylation

Feldman

Vershinin

Goliand

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Lysine methylation, catalyzed by protein lysine methyltransferases (PKMTs), is a key player in regulating intracellular signaling pathways. However, the role of PKMTs and the methylation of nonhistone proteins during the cell cycle are largely unexplored. In a recent proteomic screen, we identified that the PKMT SETD6 methylates PLK1—a key regulator of mitosis and highly expressed in tumor cells. In this study, we provide evidence that SETD6 is involved in cell cycle regulation. SETD6-deficient cells were observed to progress faster through the different mitotic steps toward the cytokinesis stage. Mechanistically, we found that during mitosis SETD6 binds and methylates PLK1 on two lysine residues: K209 and K413. Lack of methylation of these two residues results in increased kinase activity of PLK1, leading to accelerated mitosis and faster cellular proliferation, similarly to SETD6-deficient cells. Taken together, our findings reveal a role for SETD6 in regulating mitotic progression, suggesting a pathway through which SETD6 methylation activity contributes to normal mitotic pace.

show abstract

SETD6 is a negative regulator of oxidative stress response

Cited by 28 publications

References 37 publications

Chromatin associated SETD3 negatively regulates VEGF expression

Chromatin associated SETD3 negatively regulates VEGF expression

Histone Deacetylase HDA-2 Regulates Trichoderma atroviride Growth, Conidiation, Blue Light Perception, and Oxidative Stress Responses

The methyltransferase SETD6 regulates Mitotic progression through PLK1 methylation

Contact Info

Product

Resources

About