Promoting gene expression in plants by permissive histone lysine methylation

Histone lysine methylation and acetylation are important posttranslational modifications that regulate gene expression in humans. Due to the interplay of these two modifications, new chemical methods to study lysine posttranslational...

Download Full-text

Involvement of Histone Lysine Methylation in p21 Gene Expression in Rat KidneyIn Vivoand Rat Mesangial CellsIn Vitrounder Diabetic Conditions

Journal of Diabetes Research ◽

10.1155/2016/3853242 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Xiangjun Li ◽

Chaoyuan Li ◽

Xiaoxia Li ◽

Peihe Cui ◽

Qifeng Li ◽

...

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Mesangial Cells ◽

Histone H3 ◽

Diabetic Rats ◽

Lysine Methylation ◽

Histone Lysine Methylation ◽

Histone Lysine

Diabetic nephropathy (DN), a common complication associated with type 1 and type 2 diabetes mellitus (DM), characterized by glomerular mesangial expansion, inflammation, accumulation of extracellular matrix (ECM) protein, and hypertrophy, is the major cause of end-stage renal disease (ESRD). Increasing evidence suggested that p21-dependent glomerular and mesangial cell (MC) hypertrophy play key roles in the pathogenesis of DN. Recently, posttranscriptional modifications (PTMs) have uncovered novel molecular mechanisms involved in DN. However, precise regulatory mechanism of histone lysine methylation (HKme) mediating p21 related hypertrophy associated with DN is not clear. We evaluated the roles of HKme and histone methyltransferase (HMT) SET7/9 in p21 gene expression in glomeruli of diabetic rats and in high glucose- (HG-) treated rat mesangial cells (RMCs). p21 gene expression was upregulated in diabetic rats glomeruli; chromatin immunoprecipitation (ChIP) assays showed decreased histone H3-lysine9-dimethylation (H3K9me2) accompanied with enhanced histone H3-lysine4-methylation (H3K4me1/3) and SET7/9 occupancies at the p21 promoter. HG-treated RMCs exhibited increased p21 mRNA, H3K4me level, SET7/9 recruitment, and inverse H3K9me, which were reversed by TGF-β1 antibody. These data uncovered key roles of H3Kme and SET7/9 responsible for p21 gene expressionin vivoandin vitrounder diabetic conditions and confirmed preventive effect of TGF-β1 antibody on DN.

Download Full-text

Histone Lysine Methylation in TGF-β1 Mediated p21 Gene Expression in Rat Mesangial Cells

BioMed Research International ◽

10.1155/2016/6927234 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Qiaoyan Guo ◽

Xiaoxia Li ◽

Hongbo Han ◽

Chaoyuan Li ◽

Shujun Liu ◽

...

Keyword(s):

Gene Expression ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Gene Promoter ◽

Renal Diseases ◽

Lysine Methylation ◽

Histone Lysine Methylation ◽

Histone Lysine ◽

Chronic Renal Diseases

Transforming growth factor beta1- (TGF-β1-) induced p21-dependent mesangial cell (MC) hypertrophy plays a key role in the pathogenesis of chronic renal diseases including diabetic nephropathy (DN). Increasing evidence demonstrated the role of posttranscriptional modifications (PTMs) in the event; however, the precise regulatory mechanism of histone lysine methylation remains largely unknown. Here, we examined the roles of both histone H3 lysine 4 and lysine 9 methylations (H3K4me/H3K9me) in TGF-β1 induced p21 gene expression in rat mesangial cells (RMCs). Our results indicated that TGF-β1 upregulated the expression of p21 gene in RMCs, which was positively correlated with the increased chromatin marks associated with active genes (H3K4me1/H3K4me2/H3K4me3) and negatively correlated with the decreased levels of repressive marks (H3K9me2/H3K9me3) at p21 gene promoter. TGF-β1 also elevated the recruitment of the H3K4 methyltransferase (HMT) SET7/9 to the p21 gene promoter. SET7/9 gene silencing with small interfering RNAs (siRNAs) significantly abolished the TGF-β1 induced p21 gene expression. Taken together, these results reveal the key role of histone H3Kme in TGF-β1 mediated p21 gene expression in RMC, partly through HMT SET7/9 occupancy, suggesting H3Kme and SET7/9 may be potential renoprotective agents in managing chronic renal diseases.

Download Full-text

Writers and Erasers of Histone Lysine methylation with Clinically Applied Modulators: Promising Target for Cancer Therapy

Current Pharmaceutical Design ◽

10.2174/1381612822666160715125417 ◽

2016 ◽

Vol 22 (39) ◽

pp. 5943-5947 ◽

Cited By ~ 5

Author(s):

Yi-Chao Zheng ◽

Jin-Lian Ma ◽

Ying Liu ◽

Hong Liu

Keyword(s):

Cancer Therapy ◽

Lysine Methylation ◽

Histone Lysine Methylation ◽

Histone Lysine ◽

Promising Target

Download Full-text

Dynamic Patterns of Histone Lysine Methylation in the Developing Retina

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.09-4730 ◽

2010 ◽

Vol 51 (12) ◽

pp. 6784 ◽

Cited By ~ 22

Author(s):

Rajesh C. Rao ◽

Kissaou T. Tchedre ◽

Muhammad Taimur A. Malik ◽

Natasha Coleman ◽

Yuan Fang ◽

...

Keyword(s):

Lysine Methylation ◽

Histone Lysine Methylation ◽

Histone Lysine ◽

Dynamic Patterns

Download Full-text

The Indexing Potential of Histone Lysine Methylation

Reversible Protein Acetylation - Novartis Foundation Symposia ◽

10.1002/0470862637.ch3 ◽

2008 ◽

pp. 22-47 ◽

Cited By ~ 23

Author(s):

Gunnar Schotta ◽

Monika Lachner ◽

Antoine H. F. M. Peters ◽

Thomas Jenuwein

Keyword(s):

Lysine Methylation ◽

Histone Lysine Methylation ◽

Histone Lysine

Download Full-text

Protein lysine 43 methylation by EZH1 promotes AML1-ETO transcriptional repression in leukemia

Nature Communications ◽

10.1038/s41467-019-12960-6 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Liping Dou ◽

Fei Yan ◽

Jiuxia Pang ◽

Dehua Zheng ◽

Dandan Li ◽

...

Keyword(s):

Dna Sequences ◽

Transcriptional Repression ◽

Lysine Methylation ◽

Post Translational Modification ◽

Histone Lysine Methylation ◽

Histone Lysine ◽

Histone Lysine Methyltransferase ◽

Lysine Methyltransferase

Abstract The oncogenic fusion protein AML1-ETO retains the ability of AML1 to interact with the enhancer core DNA sequences, but blocks AML1-dependent transcription. Previous studies have shown that post-translational modification of AML1-ETO may play a role in its regulation. Here we report that AML1-ETO-positive patients, with high histone lysine methyltransferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. We find that EZH1 WD domain binds to the AML1-ETO NHR1 domain and methylates AML1-ETO at lysine 43 (Lys43). This requires the EZH1 SET domain, which augments AML1-ETO-dependent repression of tumor suppressor genes. Loss of Lys43 methylation by point mutation or domain deletion impairs AML1-ETO-repressive activity. These findings highlight the role of EZH1 in non-histone lysine methylation, indicating that cooperation between AML1-ETO and EZH1 and AML1-ETO site-specific lysine methylation promote AML1-ETO transcriptional repression in leukemia.

Download Full-text