The Why of YY1: Mechanisms of Transcriptional Regulation by Yin Yang 1

Verheul, Thijs C. J.; Hijfte, Levi van; Perenthaler, Elena; Barakat, Tahsin Stefan

doi:10.3389/fcell.2020.592164

Cited by 104 publications

(100 citation statements)

References 93 publications

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“…Although the role of YY1 in gene regulation has been widely studied, the mechanism of YY1 action on tumour growth is distinct in different cancers 40 . Some studies have shown that YY1 mainly acts as a tumour suppressor in pancreatic cancer, 41,42 however, most studies have shown that YY1 exists as a oncogene, such as in gastric cancer and lung cancer 43,44 .…”

Section: Discussionmentioning

confidence: 99%

Effect of lncRNA‐ATB/miR‐651‐3p/Yin Yang 1 pathway on trophoblast‐endothelial cell interaction networks

Yin

Zhang

et al. 2021

J Cellular Molecular Medi

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Our previous studies have confirmed that lncRNA‐ATB may be involved in the pathogenesis of preeclampsia, however, it is uncertain whether lncRNA‐ATB influence the interaction between trophoblast and endothelial cells, which is crucial to the uterine spiral artery remodelling. Scratch wound healing and transwell invasion assay were conducted to test the migration and invasion of trophoblast cells. Co‐culture model was used to simulate the physiological environment in vivo. The expression levels of lncRNA‐ATB were analyzed in placenta tissues from healthy pregnant women and preeclampsia patients. Subsequently, the binding site of lncRNA‐ATB and miR‐651‐3p was verified using dual‐luciferase reporter assay, and the rescue experiment was used to study the effects of these two on the biological function. The direct effects of miR‐651‐3p and Yin Yang 1 (YY1) were verified using similar methods. LncRNA‐ATB was found to be down‐regulated in the placenta of preeclampsia patients. LncRNA‐ATB knockdown decreased trophoblast migration, invasion and colocalisation with human umbilical vein endothelial cells. MiR‐651‐3p was a direct target of lncRNA‐ATB and they had opposite effects. Moreover, the expression of lncRNA‐ATB and miR‐651‐3p in placental tissues was negatively correlated. MiR‐651‐3p has been confirmed to directly target the 3′ untranslated region of YY1. The inhibitory effects of YY1 low expression on biological function was rescued by miR‐651‐3p depletion. Western blot analysis showed that lncRNA‐ATB could regulate YY1 expression by sponging miR‐651‐3p. LncRNA‐ATB functioned as a competitive endogenous RNA of miR‐651‐3p to regulate YY1 on progress of spiral artery remodelling.

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Section: Discussionmentioning

confidence: 99%

Effect of lncRNA‐ATB/miR‐651‐3p/Yin Yang 1 pathway on trophoblast‐endothelial cell interaction networks

Yin

Zhang

et al. 2021

J Cellular Molecular Medi

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“…When the structure of the repressor domain changes and its repression activity is lost. In the cell, YY1 can be transformed into an activating factor only after the N-terminal activation domain is unmasked and exposed under certain conditions [46][47][48][49] . Consistent with our conjecture, the lactylation of the lysine at position YY1 183 may cause the inhibition mechanism to fail and activate the transcriptional activity of YY1, but this hypothesis still needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2

Wang

Fan

et al. 2021

Preprint

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Ocular neovascularization is a leading cause of blindness. Retinal microglia have been implicated in hypoxia-induced angiogenesis and vasculopathy, but the underlying mechanisms remain largely unknown. Here, we report that lactylation in microglia is critical for retinal neovascularization. Using lactylome and proteomic analyses, we identified a list of hyperlactylated proteins in the context of increased lactate under hypoxia. Yin Yang-1 (YY1), a transcription factor, is lactylated at lysine 183 (K183) under hypoxia, which is regulated by p300. Furthermore, hyperlactylated YY1 directly enhances fibroblast growth factor 2 (FGF2) transcription and promotes angiogenesis. YY1 mutation at K183 eliminates these effects. Notably, clinical retrospective analysis shows that lactate concentrations in retinopathy of prematurity (ROP) infants are significantly increased compared with those in controls. Taken together, our results demonstrate that YY1 lactylation in microglia promotes FGF2 expression and plays a pivotal proangiogenic role, providing new insights into retinal neovascular diseases.

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“…For example, transcription factor YY1 (Yin Yang 1) is able to act as both a transcriptional activator and repressor, which depend on various post-translational modifications of YY1 and different co-factors binding with YY1 [ 38 , 39 , 40 ]. YY1 plays important roles in neuroprotective pathways associated with ischemic damage, Parkinson’s and Alzheimer’s disease, and acts as a tumor suppressor or stimulator [ 38 , 41 ]. Thus, whether and how PACRG interplays with these transcription regulators and transcription factors, such as YY1, would be attractive research topics.…”

Section: Discussionmentioning

confidence: 99%

Functional Expression, Purification and Identification of Interaction Partners of PACRG

et al. 2021

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PACRG (Parkin co-regulated gene) shares a bi-directional promoter with the Parkinson’s disease-associated gene Parkin, but the physiological roles of PACRG have not yet been fully elucidated. Recombinant expression methods are indispensable for protein structural and functional studies. In this study, the coding region of PACRG was cloned to a conventional vector pQE80L, as well as two cold-shock vectors pCold II and pCold-GST, respectively. The constructs were transformed into Escherichia coli (DE3), and the target proteins were overexpressed. The results showed that the cold-shock vectors are more suitable for PACRG expression. The soluble recombinant proteins were purified with Ni2+ chelating column, glutathione S-transferase (GST) affinity chromatography and gel filtration. His6 pull down assay and LC-MS/MS were carried out for identification of PACRG-binding proteins in HEK293T cell lysates, and a total number of 74 proteins were identified as potential interaction partners of PACRG. GO (Gene ontology) enrichment analysis (FunRich) of the 74 proteins revealed multiple molecular functions and biological processes. The highest proportion of the 74 proteins functioned as transcription regulator and transcription factor activity, suggesting that PACRG may play important roles in regulation of gene transcription.

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The Why of YY1: Mechanisms of Transcriptional Regulation by Yin Yang 1

Cited by 104 publications

References 93 publications

Effect of lncRNA‐ATB/miR‐651‐3p/Yin Yang 1 pathway on trophoblast‐endothelial cell interaction networks

Effect of lncRNA‐ATB/miR‐651‐3p/Yin Yang 1 pathway on trophoblast‐endothelial cell interaction networks

YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2

Functional Expression, Purification and Identification of Interaction Partners of PACRG

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