Chromatin Regulators in Pancreas Development and Diabetes

Campbell, Stephanie A.; Hoffman, Brad G.

doi:10.1016/j.tem.2015.12.005

Cited by 24 publications

(21 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three aspects are of great concern for the complete understanding of the molecular and cellular biology of the diabetic complications. First, the foremost is the phenomenon of metabolic or epigenetic memory, which refers to the remembrance of hyperglycemic episodes inducing microvascular modifications during the normal homeostasis or after glucose normalization [23,26,27]. Second, another aspect is the genetic determinants of susceptibility to macro- and microvascular complications involved in diabetic patients.…”

Section: Future Prospectsmentioning

confidence: 99%

See 1 more Smart Citation

Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy: a molecular link to regulate gene expression

Pradhan¹,

Upadhyay²,

Tiwari³

et al. 2016

New Front Ophthalmol

View full text Add to dashboard Cite

Intensification in the frequency of diabetes and the associated vascular complications has been a root cause of blindness and visual impairment worldwide. One such vascular complication which has been the prominent cause of blindness; retinal vasculature, neuronal and glial abnormalities is diabetic retinopathy (DR), a chronic complicated outcome of Type 1 and Type 2 diabetes. It has also become clear that “genetic” variations in population alone can’t explain the development and progression of diabetes and its complications including DR. DR experiences engagement of foremost mediators of diabetes such as hyperglycemia, oxidant stress, and inflammatory factors that lead to the dysregulation of “epigenetic” mechanisms involving histone acetylation and histone and DNA methylation, chromatin remodeling and expression of a complex set of stress-regulated and disease-associated genes. In addition, both elevated glucose concentration and insulin resistance leave a robust effect on epigenetic reprogramming of the endothelial cells too, since endothelium associated with the eye aids in maintaining the vascular homeostasis. Furthermore, several studies conducted on the disease suggest that the modifications of the epigenome might be the fundamental mechanism(s) for the proposed metabolic memory’ resulting into prolonged gene expression for inflammation and cellular dysfunction even after attaining the glycemic control in diabetics. Henceforth, the present review focuses on the aspects of genetic and epigenetic alterations in genes such as vascular endothelial growth factor and aldose reductase considered being associated with DR. In addition, we discuss briefly the role of the thioredoxin-interacting protein TXNIP, which is strongly induced by high glucose and diabetes, in cellular oxidative stress and mitochondrial dysfunction potentially leading to chromatin remodeling and ocular complications of diabetes. The identification of disease-associated genes and their epigenetic regulations will lead to potential new drugs and gene therapies as well as personalized medicine to prevent or slow down the progression of DR.

show abstract

Section: Future Prospectsmentioning

confidence: 99%

“…Moreover, for epigenetic mechanisms there has been various marks; one such major, countable and primary mark is DNA methylation, which involves the addition of a methyl group to the DNA fragment at nucleotide cytosine [16, 22,23]. DNA methyltransferases, DNMT1 and DNMT3A/B, use S-adenosylmethionine (SAM) as methyl donors to cytosine.…”

Section: Introductionmentioning

confidence: 99%

Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy: a molecular link to regulate gene expression

Pradhan¹,

Upadhyay²,

Tiwari³

et al. 2016

New Front Ophthalmol

View full text Add to dashboard Cite

show abstract

“…ATP-dependent chromatin remodeling complexes have essential functions during development; therefore, it is not surprising that genomic aberrations in genes encoding chromatin remodeling components contribute to different malignancies, such as cancer, including PDAC [6,32,33,35,[43][44][45]. Epigenetic reprogramming has significant roles in lineage specification during pancreas development, and the development-specific subunit expression is important for altering the functional activity of the complexes [46][47][48][49]. The majority of the studies have focused on epigenetic regulation in endocrine β-cells [46,48], and only a few reports have analyzed the role of SWI/SNF complexes in acinar and ductal cells [48,50].…”

Section: Atp-dependent Chromatin Remodeling Complexesmentioning

confidence: 99%

“…The differences in subunit compositions of each complex are associated with the cell-type, tissuespecific, or development-related roles of each complex [47,52]. SWI/SNF and INO80 subfamily complexes form large protein assemblies comprising up to 15 subunits, whereas most ISWI complexes and a subset of the CHD complexes are formed with <4 subunits.…”

Section: Atp-dependent Chromatin Remodeling Complexesmentioning

confidence: 99%

“…Additionally, SWI/SNF aberrations also modulate responsiveness to platinum-based treatment [58], indicating that detailed characterization of the human PDAC tumors can be used to identify biomarkers for improved treatment regimens. The differences in subunit compositions of each complex are associated with the cell-type, tissue-specific, or development-related roles of each complex [47,52]. SWI/SNF and INO80 subfamily complexes form large protein assemblies comprising up to 15 subunits, whereas most ISWI complexes and a subset of the CHD complexes are formed with <4 subunits.…”

Section: Swi/snf Subfamilymentioning

confidence: 99%

See 1 more Smart Citation

The Emerging Roles of ATP-Dependent Chromatin Remodeling Complexes in Pancreatic Cancer

Hasan

Ahuja

2019

Cancers

View full text Add to dashboard Cite

Pancreatic cancer is an aggressive cancer with low survival rates. Genetic and epigenetic dysregulation has been associated with the initiation and progression of pancreatic tumors. Multiple studies have pointed to the involvement of aberrant chromatin modifications in driving tumor behavior. ATP-dependent chromatin remodeling complexes regulate chromatin structure and have critical roles in stem cell maintenance, development, and cancer. Frequent mutations and chromosomal aberrations in the genes associated with subunits of the ATP-dependent chromatin remodeling complexes have been detected in different cancer types. In this review, we summarize the current literature on the genomic alterations and mechanistic studies of the ATP-dependent chromatin remodeling complexes in pancreatic cancer. Our review is focused on the four main subfamilies: SWItch/sucrose non-fermentable (SWI/SNF), imitation SWI (ISWI), chromodomain-helicase DNA-binding protein (CHD), and INOsitol-requiring mutant 80 (INO80). Finally, we discuss potential novel treatment options that use small molecules to target these complexes.

show abstract

The Potential of Epigenetic Compounds in Treating Diabetes

Gray¹

2018

Epigenetics in Human Disease

View full text Add to dashboard Cite

Chromatin Regulators in Pancreas Development and Diabetes

Cited by 24 publications

References 96 publications

Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy: a molecular link to regulate gene expression

Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy: a molecular link to regulate gene expression

The Emerging Roles of ATP-Dependent Chromatin Remodeling Complexes in Pancreatic Cancer

The Potential of Epigenetic Compounds in Treating Diabetes

Contact Info

Product

Resources

About