Unraveling the Complex Epigenetic Mechanisms that Regulate Gene Activity

Bemer, Marian

doi:10.1007/978-1-4939-7318-7_13

Cited by 12 publications

(12 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Epigenetic mechanisms are functionally essential for regulating gene expression 1,2 . Three DNA methyltransferase enzymes catalyze DNA methylation: Dnmt1, Dnmt3a, and Dnmt3b, which catalyze the transfer of a methyl group of S-adenosylmethionine (SAM) to the fifth carbon position of cytosine 26 .…”

Section: Discussionmentioning

confidence: 99%

“…Epigenetic regulation of gene expression refers to chromatin-based mechanisms that do not introduce changes in the DNA sequence per se and is not necessarily heritable. Gene-expression regulated by epigenetic modifications, such as alter DNA accessibility and chromatin structure, histone modification, and DNA methylation 1,2 . Moreover, evidence has emerged that a link exists between glutathione (GSH) metabolism and the epigenetic regulation of redox phenomena 3,4 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice

Parsanathan

Jain

2019

Sci Rep

View full text Add to dashboard Cite

Obesity has been correlating with low levels of glutathione (GSH) and 25-hydroxyvitamin D3 (25(OH)VD3). The liver is the principal site for the 25(OH)VD3 biosynthesis. This study investigated whether GSH deficiency induces epigenetic alterations that impair Vitamin D (VD) metabolism genes in the livers of HFD-fed mice. The expression of the VD metabolism genes CYP2R1 and CYP27A1 (25-hydroxylase), CYP27B1 (1-α-hydroxylase), and vitamin D receptor (VDR) were downregulated in the livers of mice fed an HFD (GSH- deficient) compared with control diet-fed group. The expression of CYP24A1 (24-hydroxylase) was significantly increased, which catabolizes both 25(OH)VD3 and 1α,25-hydroxyvitaminD3. Gene-specific hypermethylation of 25-hydroxylase, 1-α-hydroxylase, and VDR, and hypomethylation of CYP24A1 was observed in HFD-fed mice. GSH deficiency induced in cultured hepatocytes caused an increase in oxidative stress and alterations in VD regulatory genes. Similarly, elevated global DNA methylation, Dnmt activity, and 5-methylcytosine but decreased Tet activity and 5-hydroxymethylcytosine were observed in the GSH-deficient hepatocytes and the liver of HFD-fed mice. Replenishment of GSH by its prodrugs treatment beneficially altered epigenetic enzymes, and VD-metabolism genes in hepatocytes. HFD-induces GSH deficiency and epigenetically alters VD-biosynthesis pathway genes. This provides a biochemical mechanism for the VD-deficiency and potential benefits of GSH treatment in reducing 25(OH)VD3-deficiency.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice

Parsanathan

Jain

2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In land plants, LHP1 is involved in multiple basic developmental processes including organogenesis and floral transition, which has not been reported in alga. AL6/7 are H3K4me3 readers and PHD domain-containing AL proteins can recruit AtBMI1b and AtRING1ato mediate the transition from H3K4me3 to H3K27me3 [38, 102]. Furthermore, EBS/SHL functions as the H3K4me3 or H3K27me3 reader [23, 31].…”

Section: Discussionmentioning

confidence: 99%

Evolution and conservation of polycomb repressive complex 1 core components and putative associated factors in the green lineage

et al. 2019

View full text Add to dashboard Cite

Background: Polycomb group (PcG) proteins play important roles in animal and plant development and stress response. Polycomb repressive complex 1 (PRC1) and PRC2 are the key epigenetic regulators of gene expression, and are involved in almost all developmental stages. PRC1 catalyzes H2A monoubiquitination resulting in transcriptional silencing or activation. The PRC1 components in the green lineage were identified and evolution and conservation was analyzed by bioinformatics techniques. RING Finger Protein 1 (RING1), B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Like Heterochromatin Protein 1 (LHP1) and Embryonic Flower 1 (EMF1) are the PRC1 core components and Vernalization 1 (VRN1), VP1/ABI3-Like 1/2/3 (VAL1/2/3), Alfin-like 1-7 (AL1-7), Inhibitor of growth 1/2 (ING1/2), and Early Bolting in Short Days (EBS) / Short Life (SHL) are the associated factors. Results: Each PRC1 subunit possesses special domain organizations, such as RING and the ring finger and WD40associated ubiquitin-like (RAWUL) domains for RING1 and BMI1, chromatin organization modifier (CHROMO) and chromo shadow (ChSh) domains for LHP1, one or two B3 DNA binding domain(s) for VRN1, B3 and zf-CW domains for VAL1/2/3, Alfin and Plant HomeoDomain (PHD) domains for AL1-7, ING and PHD domains for ING1/2, Bromoadjacent homology (BAT) and PHD domains for EBS/SHL. Six new motifs are uncovered in EMF1. The PRC1 core components RING1 and BMI1, and the associated factors VAL1/2/3, AL1-7, ING1/2, and EBS/SHL exist from alga to higher plants, whereas LHP1 only occurs in higher plants. EMF1 and VRN1 are present only in eudicots. PRC1 components undergo duplication in the plant evolution. Most of plants carry the homologous core component LHP1, the associated factor EMF1, and several homologs in RING1, BMI1, VRN1, AL1-7, ING1/2/3, and EBS/SHL. Cabbage, cotton, poplar, orange and maize often exhibit more gene copies than other species. Domain organization analysis shows that duplicated gene functions may be of diverse. Conclusions: The PRC1 core components RING1 and BMI1, and the associated factors VAL1/2/3, AL1-7, ING1/2, and EBS/SHL originate from algae. The core component LHP1 is from moss and the associated factors EMF1 and VRN1 are from dicotyledon. PRC1 components are of functional redundancy and diversity in evolution.

show abstract

“…Chemical modification of histones is a universal theme during gene activation and can include acetylation, methylation, phosphorylation, and other post-translational events (5). Multiple studies of individual or a few genes have suggested that cofactor binding and histone modification inevitably follow activator recruitment.…”

mentioning

confidence: 99%

Frequent interferon regulatory factor 1 (IRF1) binding at remote elements without histone modification

Hassan

Huang

et al. 2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

Transcriptional activators bind DNA and recruit cofactors to modify chromatin. The extent to which these two events are separable is unclear. Here, using a custom ChIP tiling array to map chromatin modifications, we show that interferon-γ-induced DNA binding of signal transducer and activator of transcription 1 (STAT1), typically associated with the transcription factor interferon regulatory factor 1 (IRF1), causes histone acetylation (H3ac, H4ac). In contrast, among IRF1 sites lacking concomitant STAT1 recruitment, only 25% underwent inducible histone acetylation, 31% exhibited constitutive histone acetylation, and 44% had no histone acetylation. These latter "orphan sites" also lacked other activating modifications ( H3K4me1, H3K4me2) and were typically remote from transcription start sites. In these cases the closest gene was typically an IFNγ-inducible locus that did not respond to IFNγ in this setting. Orphan sites were detected in different cell types, suggesting broad relevance. Despite an atypical downstream response ( no histone modifications), IRF1 binding depended on SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4 or BRG1), as is typical of active IRF1 enhancers. Although SMARCA4 permitted IRF1 access to the orphan sites, there was no corecruitment of the histone acetyltransferases CREB-binding protein (CBP) and p300. Orphan sites were constitutively unacetylated, and several were marked with repressive chromatin modifications ( H3K27me3). In conclusion, although IRF1 can trigger enhanceosome formation independently of STAT1, its ability to do so depends on local chromatin cues.

show abstract

Unraveling the Complex Epigenetic Mechanisms that Regulate Gene Activity

Cited by 12 publications

References 137 publications

Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice

Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice

Evolution and conservation of polycomb repressive complex 1 core components and putative associated factors in the green lineage

Frequent interferon regulatory factor 1 (IRF1) binding at remote elements without histone modification

Contact Info

Product

Resources

About