Chromatin

Gross, David S.; Chowdhary, Surabhi; Anandhakumar, Jayamani; Kainth, Amoldeep S.

doi:10.1016/j.cub.2015.10.059

Cited by 13 publications

(13 citation statements)

References 17 publications

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“…These differences are likely to be partly due to the restricted site of interaction between plastic-bound NETs and the nearby partial surface of the islet versus the greater accessibility for free histones (in suspension) to interact with the entire islet surface. In addition, since there exists a 1:1 ratio of DNA to protein in chromatin ( 46 ), the histone content of PMA- and CI-NETs (with DNA content ≤ 1 μg /mL) was much lower than for free calf thymus histones (200–800 μg/mL), resulting in less toxicity for the islets. Nevertheless, this study demonstrated significant NET-induced toxicity for mouse islets in vitro.…”

Section: Resultsmentioning

confidence: 99%

Circulating platelet-neutrophil aggregates characterize the development of type 1 diabetes in humans and NOD mice

Popp¹,

Vecchio²,

Brown³

et al. 2022

JCI Insight

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Section: Resultsmentioning

confidence: 99%

Circulating platelet-neutrophil aggregates characterize the development of type 1 diabetes in humans and NOD mice

Popp¹,

Vecchio²,

Brown³

et al. 2022

JCI Insight

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“…The greater than twofold increase in transcription from a tandem duplicate could arise from aspects of various known regulatory mechanisms. Some of the possibilities we can envision include the following: (i) more frequent rebinding of transcription factors because the local concentration of binding sites is higher in tandemly arranged duplicates (18); (ii) more efficient looping of DNA due to clusters of transcription factors binding to identical sites on both gene copies (18); or (iii) more effective remodeling of chromatin to a favorable state for transcription (19). Any of these mechanisms could be enhanced or attenuated by neighboring sequences (i.e., by classical position effects), which could account for the observed dependence of the degree of overactivity on chromosomal position.…”

Section: The Biological Significance and Potential Mechanisms Underlyingmentioning

confidence: 99%

Expression of tandem gene duplicates is often greater than twofold

Loehlin

Carroll

2016

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

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Tandem gene duplication is an important mutational process in evolutionary adaptation and human disease. Hypothetically, two tandem gene copies should produce twice the output of a single gene, but this expectation has not been rigorously investigated. Here, we show that tandem duplication often results in more than double the gene activity. A naturally occurring tandem duplication of the Alcohol dehydrogenase (Adh) gene exhibits 2.6-fold greater expression than the single-copy gene in transgenic Drosophila. This tandem duplication also exhibits greater activity than two copies of the gene in trans, demonstrating that it is the tandem arrangement and not copy number that is the cause of overactivity. We also show that tandem duplication of an unrelated synthetic reporter gene is overactive (2.3- to 5.1-fold) at all sites in the genome that we tested, suggesting that overactivity could be a general property of tandem gene duplicates. Overactivity occurs at the level of RNA transcription, and therefore tandem duplicate overactivity appears to be a previously unidentified form of position effect. The increment of surplus gene expression observed is comparable to many regulatory mutations fixed in nature and, if typical of other genomes, would shape the fate of tandem duplicates in evolution.

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“…Histones, especially their N-terminal tails (containing an average of 15–30 residues), can undergo a plethora of PTMs, such as acetylation, methylation, phosphorylation, and more rarely, ubiquitination, sumoylation, and glycosylation [ 58 ]. The acetylation (ac) of histone lysines (K), is associated with the transition to an “open” conformation; this weakens DNA–histone interactions, increases DNA accessibility, and facilitates transcription.…”

Section: Epigenetics: Another Layer Of Information In Gene Expression Regulationmentioning

confidence: 99%

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

Dobre

Constantin

Costache

et al. 2021

JPM

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Epigenetic alterations have emerged as essential contributors in the pathogenesis of various human diseases, including cutaneous melanoma (CM). Unlike genetic changes, epigenetic modifications are highly dynamic and reversible and thus easy to regulate. Here, we present a comprehensive review of the latest research findings on the role of genetic and epigenetic alterations in CM initiation and development. We believe that a better understanding of how aberrant DNA methylation and histone modifications, along with other molecular processes, affect the genesis and clinical behavior of CM can provide the clinical management of this disease a wide range of diagnostic and prognostic biomarkers, as well as potential therapeutic targets that can be used to prevent or abrogate drug resistance. We will also approach the modalities by which these epigenetic alterations can be used to customize the therapeutic algorithms in CM, the current status of epi-therapies, and the preliminary results of epigenetic and traditional combinatorial pharmacological approaches in this fatal disease.

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Chromatin

Cited by 13 publications

References 17 publications

Circulating platelet-neutrophil aggregates characterize the development of type 1 diabetes in humans and NOD mice

Circulating platelet-neutrophil aggregates characterize the development of type 1 diabetes in humans and NOD mice

Expression of tandem gene duplicates is often greater than twofold

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

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