scholarly journals The Impact of the HydroxyMethylCytosine epigenetic signature on DNA structure and function

2021 ◽  
Vol 17 (11) ◽  
pp. e1009547
Author(s):  
Federica Battistini ◽  
Pablo D. Dans ◽  
Montserrat Terrazas ◽  
Chiara L. Castellazzi ◽  
Guillem Portella ◽  
...  
Keyword(s):  
Physical Properties ◽  
Cytosine Methylation ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Lower Ability ◽  
Dual Activation ◽  
Activation Pathways ◽  
And Function ◽  
The Impact ◽  
Rule Out

We present a comprehensive, experimental and theoretical study of the impact of 5-hydroxymethylation of DNA cytosine. Using molecular dynamics, biophysical experiments and NMR spectroscopy, we found that Ten-Eleven translocation (TET) dioxygenases generate an epigenetic variant with structural and physical properties similar to those of 5-methylcytosine. Experiments and simulations demonstrate that 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC) generally lead to stiffer DNA than normal cytosine, with poorer circularization efficiencies and lower ability to form nucleosomes. In particular, we can rule out the hypothesis that hydroxymethylation reverts to unmodified cytosine physical properties, as hmC is even more rigid than mC. Thus, we do not expect dramatic changes in the chromatin structure induced by differences in physical properties between d(mCpG) and d(hmCpG). Conversely, our simulations suggest that methylated-DNA binding domains (MBDs), associated with repression activities, are sensitive to the substitution d(mCpG) ➔ d(hmCpG), while MBD3 which has a dual activation/repression activity is not sensitive to the d(mCpG) d(hmCpG) change. Overall, while gene activity changes due to cytosine methylation are the result of the combination of stiffness-related chromatin reorganization and MBD binding, those associated to 5-hydroxylation of methylcytosine could be explained by a change in the balance of repression/activation pathways related to differential MBD binding.

scholarly journals The Impact of The Hydroxymethyl-Cytosine Epigenetic Signature on DNA Structure And Function

2020 ◽  
Author(s):  
Federica Battistini ◽  
Pablo D. Dans ◽  
Montserrat Terrazas ◽  
Chiara L. Castellazzi ◽  
Guillem Portella ◽  
...  
Keyword(s):  
Physical Properties ◽  
Cytosine Methylation ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Hydroxymethyl Cytosine ◽  
Lower Ability ◽  
Dual Activation ◽  
Activation Pathways ◽  
And Function ◽  
The Impact

ABSTRACTWe present a comprehensive, experimental and theoretical study of the impact of 5-hydroxymethylation of DNA cytosine. Using molecular dynamics, biophysical experiments and NMR spectroscopy, we found that Ten-Eleven translocation (TET) dioxygenases generate an epigenetic variant with structural and physical properties not too different to those of 5-methylcytosine. Experiments and simulations demonstrate that 5-methyl-cytosine (mC) and 5-hydroxymethyl-cytosine (hmC) generally lead to more rigid duplexes with poorer circularization efficiencies and lower ability to form nucleosomes. In particular, we can rule out the hypothesis that hydroxymethylation reverts to unmodified cytosine physical properties, as hmC is even more rigid than mC. Thus, we do not expect dramatic changes in the chromatin structure induced by differences in physical properties between d(mCpG) and d(hmCpG). On the contrary, our simulations suggest that methylated-DNA binding domains (MBD), associated with repression activities, are very sensitive to the substitution d(mCpG)→ d(hmCpG), while MBD3 which has a dual activation/repression activity is not sensitive to the d(mCpG) → d(hmCpG) change. Overall, while changes in gene activity due to cytosine methylation are the result of the combination of stiffness-related chromatin reorganization and MBD binding, those associated to 5-hydroxylation of methylcytosine could be explained by a change in the balance of repression/activation pathways related to differential MBD binding.

scholarly journals Nrg1 and Nrg2 Transcriptional Repressors Are Differently Regulated in Response to Carbon Source

2004 ◽  
Vol 3 (2) ◽  
pp. 311-317 ◽  
Author(s):  
Cristin D. Berkey ◽  
Valmik K. Vyas ◽  
Marian Carlson
Keyword(s):  
Carbon Source ◽  
Carbon Sources ◽  
Large Set ◽  
Transcriptional Repressors ◽  
Glucose Limitation ◽  
Dna Binding Domains ◽  
Protein Levels ◽  
Binding Domains ◽  
And Function ◽  
Mutant Cells

ABSTRACT The Nrg1 and Nrg2 repressors of Saccharomyces cerevisiae have highly similar zinc fingers and closely related functions in the regulation of glucose-repressed genes. We show that NRG1 and NRG2 are differently regulated in response to carbon source at both the RNA and protein levels. Expression of NRG1 RNA is glucose repressed, whereas NRG2 RNA levels are nearly constant. Nrg1 protein levels are elevated in response to glucose limitation or growth in nonfermentable carbon sources, whereas Nrg2 levels are diminished. Chromatin immunoprecipitation assays showed that Nrg1 and Nrg2 bind DNA both in the presence and absence of glucose. In mutant cells lacking the corepressor Ssn6(Cyc8)-Tup1, promoter-bound Nrg1, but not Nrg2, functions as an activator in a reporter assay, providing evidence that the two Nrg proteins have distinct properties. We suggest that the differences in expression and function of these two repressors, in combination with their similar DNA-binding domains, contribute to the complex regulation of the large set of glucose-repressed genes.

scholarly journals The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma

2020 ◽  
Vol 27 (9) ◽  
pp. 836-845 ◽  
Author(s):  
Matthew J. McBride ◽  
Nazar Mashtalir ◽  
Evan B. Winter ◽  
Hai T. Dao ◽  
Martin Filipovski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synovial Sarcoma ◽  
Direct Interaction ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Selective Targeting ◽  
Associated Proteins ◽  
And Function ◽  
Genomic Regions ◽  
Nucleosome Binding

AbstractInteractions between chromatin-associated proteins and the histone landscape play major roles in dictating genome topology and gene expression. Cancer-specific fusion oncoproteins, which display unique chromatin localization patterns, often lack classical DNA-binding domains, presenting challenges in identifying mechanisms governing their site-specific chromatin targeting and function. Here we identify a minimal region of the human SS18-SSX fusion oncoprotein (the hallmark driver of synovial sarcoma) that mediates a direct interaction between the mSWI/SNF complex and the nucleosome acidic patch. This binding results in altered mSWI/SNF composition and nucleosome engagement, driving cancer-specific mSWI/SNF complex targeting and gene expression. Furthermore, the C-terminal region of SSX confers preferential affinity to repressed, H2AK119Ub-marked nucleosomes, underlying the selective targeting to polycomb-marked genomic regions and synovial sarcoma–specific dependency on PRC1 function. Together, our results describe a functional interplay between a key nucleosome binding hub and a histone modification that underlies the disease-specific recruitment of a major chromatin remodeling complex.

scholarly journals Genome-wide chromatin binding of transcriptional corepressor Topless-related 1 in Arabidopsis

2020 ◽  
Author(s):  
Thomas Griebel ◽  
Dmitry Lapin ◽  
Barbara Kracher ◽  
Lorenzo Concia ◽  
Moussa Benhamed ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Plant Responses ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Genome Wide ◽  
Gene Expression Control ◽  
Specific Regulation ◽  
Transcriptional Corepressors ◽  
And Function

AbstractTimely and specific regulation of gene expression is critical for plant responses to environmental and developmental cues. Transcriptional coregulators have emerged as important factors in gene expression control, although they lack DNA-binding domains and the mechanisms by which they are recruited to and function at the chromatin are poorly understood. Plant Topless-related 1 (TPR1), belonging to a family of transcriptional corepressors found across eukaryotes, contributes to immunity signaling in Arabidopsis thaliana and wild tobacco. We performed chromatin immunoprecipitation and sequencing (ChIP-seq) on an Arabidopsis TPR1-GFP expressing transgenic line to characterize genome-wide TPR1-chromatin associations. The analysis revealed ∼1400 genes bound by TPR1, with the majority of binding sites located at gene upstream regions. Among the TPR1 bound genes, we find not only regulators of immunity but also genes controlling growth and development. To support further analysis of TPR1-chromatin complexes and other transcriptional corepressors in plants, we provide two ways to access the processed ChIP-seq data and enable their broader use by the research community.

scholarly journals Layered roles of fruitless isoforms in specification and function of male aggression-promoting neurons in Drosophila

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Margot Wohl ◽  
Kenichi Ishii ◽  
Kenta Asahina
Keyword(s):  
Aggressive Behavior ◽  
Neural Circuit ◽  
Courtship Behavior ◽  
Dominant Role ◽  
Sexually Dimorphic ◽  
Dna Binding Domains ◽  
Male Type ◽  
Binding Domains ◽  
And Function

Inter-male aggressive behavior is a prominent sexually dimorphic behavior. Neural circuits that underlie aggressive behavior are therefore likely under the control of sex-determining genes. However, the neurogenetic mechanism that generates sex-specific aggressive behavior remains largely unknown. Here, we found that a neuronal class specified by one of the Drosophila sex determining genes, fruitless (fru), belongs to the neural circuit that generates male-type aggressive behavior. This neuronal class can promote aggressive behavior independent of another sex determining gene, doublesex (dsx), although dsx is involved in ensuring that aggressive behavior is performed only toward males. We also found that three fru isoforms with different DNA binding domains show a division of labor on male aggressive behaviors. A dominant role of fru in specifying sex-specific aggressive behavior may underscore a genetic mechanism that allows male-type aggressive behavior to evolve at least partially independently from courtship behavior, which is under different selective pressures.

Surgery for Lung Cancer and the Consequences for the Swallow

2016 ◽  
Vol 1 (13) ◽  
pp. 162-168
Author(s):  
Pippa Hales ◽  
Corinne Mossey-Gaston
Keyword(s):  
Lung Cancer ◽  
Treatment Options ◽  
Vocal Cord Palsy ◽  
Subsequent Treatment ◽  
Physiological Reserve ◽  
Palliative Phase ◽  
And Function ◽  
The Impact ◽  
Swallow Function

Lung cancer is one of the most commonly diagnosed cancers across Northern America and Europe. Treatment options offered are dependent on the type of cancer, the location of the tumor, the staging, and the overall health of the person. When surgery for lung cancer is offered, difficulty swallowing is a potential complication that can have several influencing factors. Surgical interaction with the recurrent laryngeal nerve (RLN) can lead to unilateral vocal cord palsy, altering swallow function and safety. Understanding whether the RLN has been preserved, damaged, or sacrificed is integral to understanding the effect on the swallow and the subsequent treatment options available. There is also the risk of post-surgical reduction of physiological reserve, which can reduce the strength and function of the swallow in addition to any surgery specific complications. As lung cancer has a limited prognosis, the clinician must also factor in the palliative phase, as this can further increase the burden of an already compromised swallow. By understanding the surgery and the implications this may have for the swallow, there is the potential to reduce the impact of post-surgical complications and so improve quality of life (QOL) for people with lung cancer.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

Does kraft hardwood and softwood pulp viscosity correlate to paper properties?

TAPPI Journal ◽  
2016 ◽  
Vol 15 (10) ◽  
pp. 643-651 ◽  
Author(s):  
ROBERT J. OGLESBY ◽  
HUMPHREY J. MOYNIHAN ◽  
RICARDO B. SANTOS ◽  
ASHOK GHOSH ◽  
PETER W. HART
Keyword(s):  
Physical Properties ◽  
Strength Loss ◽  
Strength Properties ◽  
Clear Correlation ◽  
Paper Properties ◽  
Physical Strength ◽  
Pulp Viscosity ◽  
Softwood Pulp ◽  
The Impact ◽  
Related Paper

The impact of commercially prepared, fully bleached pulp viscosity variation on handsheet physical properties was evaluated at different levels of pulp refining. Hardwood pulps from the same brownstock species mix, cooking parameters, and kappa numbers were processed through two different commercial bleach plants: one with a D0(EP)D1D2 sequence and the second with an OD0(EOP)D1 sequence. Additionally, a commercial softwood (predominately Scotts pine) brownstock pulp bleached by an OD0(EP)D1D2 sequence was employed in this study. Pulps with viscosities ranging from 14 to 21 mPa∙s were refined in a Valley beater to two freeness levels, and the associated handsheet physical properties were measured in this study. Over the pulp viscosity range of 14 to 21 mPa∙s, no clear correlation was found to exist between pulp viscosity and related paper physical properties. Finally, a series of laboratory prepared bleached pulps were purposely prepared under non-ideal conditions to reduce their final viscosities to lower values. Handsheets made from these pulps were tested in their unbeaten condition for physical strength properties. Significant and rapid strength loss occurred when the measured pulp viscosity dropped below 12 mPa∙s; overall strength properties showed no correlation to viscosity above the critical 12 mPa∙s value.

Investigating Burnt Mounds in Clydesdale during Motorway Construction

1998 ◽  
Vol 21 (1) ◽  
pp. 1-28
Author(s):  
John A Atkinson ◽  
Camilla Dickson ◽  
Jane Downes ◽  
Paul Robins ◽  
David Sanderson
Keyword(s):  
Bronze Age ◽  
Research Strategy ◽  
Archaeological Evidence ◽  
Radiocarbon Dates ◽  
Short Account ◽  
And Function ◽  
The Impact ◽  
The Bronze Age

Summary Two small burnt mounds were excavated as part of the programme to mitigate the impact of motorway construction in the Crawford area. The excavations followed a research strategy designed to address questions of date and function. This paper surveys the various competing theories about burnt mounds and how the archaeological evidence was evaluated against those theories. Both sites produced radiocarbon dates from the Bronze Age and evidence to suggest that they were cooking places. In addition, a short account is presented of two further burnt mounds discovered during the construction of the motorway in Annandale.

Modernism, Empiricism, and Rationalism

2016 ◽  
Vol 46 (1) ◽  
pp. 38-47
Author(s):  
Geoffrey Squires
Keyword(s):  
Twentieth Century ◽  
The Other ◽  
Modern Poetry ◽  
Philosophical Perspective ◽  
Irish Poetry ◽  
Dimensional Spectrum ◽  
Culture History ◽  
The World ◽  
The Impact ◽  
Rule Out

Modernism is usually defined historically as the composite movement at the beginning of the twentieth century which led to a radical break with what had gone before in literature and the other arts. Given the problems of the continuing use of the concept to cover subsequent writing, this essay proposes an alternative, philosophical perspective which explores the impact of rationalism (what we bring to the world) on the prevailing empiricism (what we take from the world) of modern poetry, which leads to a concern with consciousness rather than experience. This in turn involves a re-conceptualisation of the lyric or narrative I, of language itself as a phenomenon, and of other poetic themes such as nature, culture, history, and art. Against the background of the dominant empiricism of modern Irish poetry as presented in Crotty's anthology, the essay explores these ideas in terms of a small number of poets who may be considered modernist in various ways. This does not rule out modernist elements in some other poets and the initial distinction between a poetics of experience and one of consciousness is better seen as a multi-dimensional spectrum that requires further, more detailed analysis than is possible here.

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