Profiles of Epigenetic Histone Post-translational Modifications at Type 1 Diabetes Susceptible Genes

Miao, Feng; Chen, Zhuo; Zhang, Lingxiao; Liu, Zheng; Wu, Xiwei; Yuan, Yate-Ching; Natarajan, Rama

doi:10.1074/jbc.m111.330373

Cited by 94 publications

(76 citation statements)

References 52 publications

(64 reference statements)

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“…Analysis of public ChIP-chip microarray data of lymphocytes using anti-H4K16Ac, H3K9Ac, and H3K9me3 showed that these PTMs differentially regulated transcription of CD14, CD11c, and CD11b (53). Acetylation of H4K16 specifically increases transcription at the CD11b gene, acetylation of H3K9 specifically increases transcription at the CD14 and CD11c genes, and tri-methylation of H3K9 increases transcription at the CD11c gene but decreases transcription at the CD11b gene (supplemental Fig.…”

Section: Proper Regulation Of Histone Acetylation Is Required For Monmentioning

confidence: 99%

Quantitative Proteomics Reveals a Role for Epigenetic Reprogramming During Human Monocyte Differentiation

Nicholas

Tang²,

Zhang

et al. 2015

Molecular & Cellular Proteomics

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The differentiation of monocytes into macrophages and dendritic cells involves mechanisms for activation of the innate immune system in response to inflammatory stimuli, such as pathogen infection and environmental cues. Epigenetic reprogramming is thought to play an important role during monocyte differentiation. Complementary to cell surface markers, the characterization of monocytic cell lineages by mass spectrometry based protein/histone expression profiling opens a new avenue for studying immune cell differentiation. Here, we report the application of mass spectrometry and bioinformatics to identify changes in human monocytes during their differentiation into macrophages and dendritic cells. Our data show that linker histone H1 proteins are significantly down-regulated during monocyte differentiation. Although highly enriched H3K9-methyl/S10-phos/K14-acetyl tri-modification forms of histone H3 were identified in monocytes and macrophages, they were dramatically reduced in dendritic cells. In contrast, histone H4 K16 acetylation was found to be markedly higher in dendritic cells than in monocytes and macrophages. We also found that global hyperacetylation generated by the nonspecific histone deacetylase HDAC inhibitor Apicidin induces monocyte differentiation. Together, our data suggest that specific regulation of inter-and intra-histone modifications including H3 K9 methylation, H3 S10 phosphorylation, H3 K14 acetylation, and H4 K16 acetylation must occur in concert with chromatin remodeling by linker histones for cell cycle progression and differentiation of human myeloid cells into macrophages and dendritic cells. Molecular & Cellular

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Section: Proper Regulation Of Histone Acetylation Is Required For Monmentioning

confidence: 99%

Quantitative Proteomics Reveals a Role for Epigenetic Reprogramming During Human Monocyte Differentiation

Nicholas

Tang²,

Zhang

et al. 2015

Molecular & Cellular Proteomics

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“…By profiling key epigenetic histone PTM marks in HG-treated human monocytes using ChIP-chips, we previously identified genes and chromatin regions in which histone methylation levels were altered by chronic HG as well as their correlation with gene expression (34). Using the same ChIPchip technology in peripheral blood monocytes and lymphocytes obtained from T1D patients and healthy controls, we also found genomic regions that had differential levels of several histones PTMs (31,33). Another study using next-generation sequencing reported genome-wide changes in DNA methylation and histone H3 lysine 9/14 acetylation (H3K9/K14Ac) in HG-treated human endothelial cells, which revealed several known and novel genes and pathways associated with endothelial dysfunction (38).…”

mentioning

confidence: 93%

RNA-sequencing analysis of high glucose-treated monocytes reveals novel transcriptome signatures and associated epigenetic profiles

Miao

Chen

Zhang

et al. 2013

Physiological Genomics

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R. RNA-sequencing analysis of high glucose-treated monocytes reveals novel transcriptome signatures and associated epigenetic profiles. Physiol Genomics 45: 287-299, 2013. First published February 5, 2013 doi:10.1152/physiolgenomics.00001.2013.-We performed high throughput transcriptomic profiling with RNA sequencing (RNA-Seq) to uncover network responses in human THP-1 monocytes treated with high glucose (HG). Our data analyses revealed that interferon (IFN) signaling, pattern recognition receptors, and activated interferon regulatory factors (IRFs) were enriched among the HGupregulated genes. Motif analysis identified an HG-responsive IRFmediated network in which interferon-stimulated genes (ISGs) were enriched. Notably, this network showed strong overlap with a recently discovered IRF7-driven network relevant to Type 1 diabetes. We next examined if the HG-regulated genes possessed any characteristic chromatin features in the basal state by profiling 15 active and repressive chromatin marks under normal glucose conditions using chromatin immunoprecipitation linked to promoter microarrays. Composite profiles revealed higher histone H3 lysine-9-acetylation levels around the promoters of HG-upregulated genes compared with all RefSeq promoters. Interestingly, within the HG-upregulated genes, active chromatin marks were enriched not only at high CpG content promoters, but surprisingly also at low CpG content promoters. Similar results were obtained with peripheral blood monocytes exposed to HG. These new results reveal a novel mechanism by which HG can exercise IFN-␣-like effects in monocytes by upregulating a set of ISGs poised for activation with multiple chromatin marks. high glucose; monocytes; diabetic complications; interferon regulatory factors; chromatin state CHRONIC HYPERGLYCEMIA OR GLUCOSE toxicity associated with both Type 1 (T1D) and Type 2 diabetes has been attributed to the development of various complications including cardiovascular disease, neuropathy, nephropathy, and retinopathy (7,8,17,48). These complications can result from the adverse effects of high glucose (HG) on many fundamental biological processes in target tissues and cells. As the soaring rates of diabetes and its complications have become major health care issues, it is imperative to examine the underlying mechanisms by evaluating signaling molecules, networks, genetic, and epigenetic elements that contribute to the relevant deregulated pathways using emerging new technologies.Several biochemical mechanisms have been implicated in hyperglycemia-induced cellular damage (7,8), including increased oxidant stress, activation of protein kinase C and other signaling kinases, as well as formation of advanced glycation end products. Evidence also shows that the expression of inflammatory cytokines and chemokines, Toll-like receptors, and many signaling molecules are affected by HG in primary human monocytes and THP-1 monocytes (5,10,11,13,20,24,32,(45)(46)(47)53) and that this leads to the impairment of key biological pathways. Despite the...

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“…Several laboratories, including our laboratory, using cell and animal models have suggested roles for key histone PTMs in high glucose (HG)-mediated effects, diabetic complications, and metabolic memory (9,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Histone PTM profiling of vascular and inflammatory cells cultured with HG vs. normal glucose (NG) or WBCs from T1D patients vs. healthy volunteers or T1D patients with complications vs. those without depicted significant PTM differences and candidate differentially methylated or acetylated genes relevant to diabetes or its complications (23,(32)(33)(34).…”

mentioning

confidence: 99%

Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort

Chen

Miao

Paterson

et al. 2016

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

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185

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We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term followup Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P < 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein (TXNIP), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory.T he landmark Diabetes Control and Complications Trial (DCCT; 1983-1993 clearly showed that intensive (INT) glycemic control profoundly reduces the development and progression of microvascular complications in type 1 diabetes (T1D). The DCCT participants were subsequently followed in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study (1994 to present), during which all subjects were advised to practice INT treatment. Surprisingly, those previously assigned to conventional (CONV) therapy continued to develop complications, such as nephropathy, retinopathy, and macrovascular diseases, at significantly higher rates than the previous INT therapy group, despite nearly similar HbA1c levels during the EDIC Study (1-3). This persistence of benefit from early application of INT therapy, called "metabolic memory," is an enigma in the field of T1D: recent studies have suggested the involvement of epigenetic mechanisms (4-9).Epigenetics is the study of mostly heritable changes in gene expression and phenotype that occur without alterations in the underlying DNA sequence. Epigenetic states are affected by environmental factors, such as aberrant nutrition and metabolic states (4, 6-8, 10). DNA methylation (DNA-me; the classic epigenetic mark) and posttranslational modifications (PTMs) of histo...

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Profiles of Epigenetic Histone Post-translational Modifications at Type 1 Diabetes Susceptible Genes

Cited by 94 publications

References 52 publications

Quantitative Proteomics Reveals a Role for Epigenetic Reprogramming During Human Monocyte Differentiation

Quantitative Proteomics Reveals a Role for Epigenetic Reprogramming During Human Monocyte Differentiation

RNA-sequencing analysis of high glucose-treated monocytes reveals novel transcriptome signatures and associated epigenetic profiles

Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort

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