scholarly journals ATP-dependent chromatin remodeling complexes in embryonic vascular development and hypertension

2019 ◽  
Vol 317 (3) ◽  
pp. H575-H580
Author(s):  
Patrick L. Crosswhite
Keyword(s):  
Blood Pressure ◽  
Therapeutic Approaches ◽  
Chromatin Remodeler ◽  
Chromatin Remodelers ◽  
Preventable Risk Factor ◽  
Hypertensive Animal ◽  
Genomic Studies ◽  
Chromatin Remodeling Complexes ◽  
Embryonic Vascular Development ◽  
As Stress

Hypertension, a chronic elevation in blood pressure, is the largest single contributing factor to mortality worldwide and the most common preventable risk factor for cardiovascular disease. High blood pressure increases the risk for someone to experience a number of adverse cardiovascular events including heart failure, stroke, or aneurysm. Despite advancements in understanding factors that contribute to hypertension, the etiology remains elusive and there remains a critical need to develop innovative study approaches to develop more effective therapeutics. ATP-dependent chromatin remodelers are dynamic regulators of DNA-histone bonds and thus gene expression. The goal of this review is to highlight and summarize reports of ATP-dependent chromatin remodelers contribution to the development or maintenance of hypertension. Emerging evidence from hypertensive animal models suggests that induction of chromatin remodeler activity increases proinflammatory genes and increases blood pressure, whereas human studies demonstrate how chromatin remodelers may act as stress-response sensors to harmful physiological stimuli. Importantly, genomic studies have linked patients with hypertension to mutations in chromatin remodeler genes. Collectively, evidence linking chromatin remodelers and hypertension warrants additional research and ultimately could reveal novel therapeutic approaches for treating this complex and devastating disease.

scholarly journals ARID2 Chromatin Remodeler in Hepatocellular Carcinoma

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2152
Author(s):  
Robin Loesch ◽  
Linda Chenane ◽  
Sabine Colnot
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Associated Factors ◽  
Regulation Of Gene Expression ◽  
Specific Gene ◽  
Chromatin Remodeler ◽  
Chromatin Remodelers ◽  
Genes Encoding ◽  
Gene Alterations

Chromatin remodelers are found highly mutated in cancer including hepatocellular carcinoma. These mutations frequently occur in ARID (AT-rich Interactive Domain) genes, encoding subunits of the ATP-dependent SWI/SNF remodelers. The increasingly prevalent complexity that surrounds the functions and specificities of the highly modular BAF (BG1/BRM-associated factors) and PBAF (polybromo-associated BAF) complexes, including ARID1A/B or ARID2, is baffling. The involvement of the SWI/SNF complexes in diverse tissues and processes, and especially in the regulation of gene expression, multiplies the specific outcomes of specific gene alterations. A better understanding of the molecular consequences of specific mutations impairing chromatin remodelers is needed. In this review, we summarize what we know about the tumor-modulating properties of ARID2 in hepatocellular carcinoma.

scholarly journals Androgen versus erythropoietin for the treatment of anemia in hemodialyzed patients: a prospective study.

1996 ◽  
Vol 7 (1) ◽  
pp. 140-144
Author(s):  
J L Teruel ◽  
R Marcen ◽  
J Navarro-Antolin ◽  
A Aguilera ◽  
G Fernandez-Juarez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Recombinant Human Erythropoietin ◽  
Dry Weight ◽  
Pressure Control ◽  
Therapeutic Approaches ◽  
Human Erythropoietin ◽  
Group A ◽  
Male Patients ◽  
Group B ◽  
A Prospective Study

According to this facility's protocol for the treatment of anemia in hemodialyzed patients, androgens were administered to male patients aged over 50 yr and recombinant human erythropoietin was administered to male patients below 50 yr of age and to female patients. In the study presented here, both therapeutic approaches have been prospectively analyzed. Patients were divided into two groups. Group A was composed of 18 patients, aged 62 +/- 12 yr, treated with nandrolone decanoate (200 mg/wk im) for 6 months; Group B was composed of 22 patients (6 men, 16 women) aged 47 +/- 15 yr, treated with subcutaneous recombinant human erythropoietin (initial dose, 6000 IU/wk) for 6 months. The increases of hemoglobin were similar in both groups; Group A, from 7.3 +/- 0.8 to 10.8 +/- 1.7 g/dL (P < 0.001), and Group B, from 7 +/- 0.6 to 10.4 +/- 1 g/dL (P < 0.001). In Group A, increases of triglycerides (159 +/- 71 versus 267 +/- 153 mg/dL, P < 0.001), serum albumin (3.9 +/- 0.3 versus 4.2 +/- 0.3 g/dL, P < 0.05), and dry weight (62.1 +/- 9.8 versus 64.9 +/- 10.1 kg, P < 0.001) were observed, which remained unmodified in Group B. Blood pressure control worsened in one patient (6%) from Group A, and in ten patients (45%) from Group B (P < 0.05). In conclusion, androgens produced an improvement in anemia in selected patients, similar to that achieved by use of recombinant human erythropoietin but at a lower cost. Androgens also have an appreciable anabolic effect and did not increase the blood pressure.

Abstract P124: Blood Pressure Characterization In Btg2 Mutant Rat

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Matthew Hoffman ◽  
Akiko Takizawa ◽  
Eric Jensen ◽  
Rebecca Schilling ◽  
Michael Grzybowski ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Signaling Pathways ◽  
Complex Disease ◽  
Cell Cycle Gene ◽  
Dietary Salt ◽  
Genetic Determinants ◽  
Therapeutic Approaches ◽  
Skeletal Morphology ◽  
Environmental Interactions ◽  
Modifiable Factors

Hypertension (HTN) is a complex disease influenced by heritable genetic elements and environmental interactions. Dietary salt is among the most influential modifiable factors contributing to increased blood pressure (BP). It is well established that men and women develop BP impairment in different patterns and a recent emphasis has been placed on identifying mechanisms leading to the differences observed between the sexes in HTN development. The current work reported here builds on an extensive genetic mapping experiment which sought to identify genetic determinants of salt sensitive (SS) HTN using the Dahl SS rat. BTG anti-proliferation factor 2 ( Btg2 ) was previously isolated by our group using congenic breeding experiments which identified it as a female causative SS HTN candidate gene. In the current study, Btg2 was mutated using TALEN targeted gene disruption on the SSBN congenic rat background. The Btg2 mutated rats exhibited impaired BP and proteinuria responses to a high salt diet compared to wild type littermates. Differences in body weight, mutant pup viability, skeletal morphology, and adult nephron density suggest a potential role for Btg2 in developmental signaling pathways. Subsequent cell cycle gene expression assessment provides several additional signaling pathways that Btg2 may function through during salt handling in the kidney. The expression analysis also indicates several upstream targets that can be explored to further isolate therapeutic approaches for SS HTN.

scholarly journals GBAF, a small BAF sub-complex with big implications: a systematic review

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Sarah M. Innis ◽  
Birgit Cabot
Keyword(s):  
Chromatin Remodeling ◽  
Cellular Differentiation ◽  
Complex Function ◽  
Therapeutic Interventions ◽  
Mammalian Development ◽  
Aberrant Expression ◽  
Chromatin Remodelers ◽  
Baf Complex ◽  
Chromatin Remodeling Complexes ◽  
Histone Modifying Enzymes

Abstract ATP-dependent chromatin remodeling by histone-modifying enzymes and chromatin remodeling complexes is crucial for maintaining chromatin organization and facilitating gene transcription. In the SWI/SNF family of ATP-dependent chromatin remodelers, distinct complexes such as BAF, PBAF, GBAF, esBAF and npBAF/nBAF are of particular interest regarding their implications in cellular differentiation and development, as well as in various diseases. The recently identified BAF subcomplex GBAF is no exception to this, and information is emerging linking this complex and its components to crucial events in mammalian development. Furthermore, given the essential nature of many of its subunits in maintaining effective chromatin remodeling function, it comes as no surprise that aberrant expression of GBAF complex components is associated with disease development, including neurodevelopmental disorders and numerous malignancies. It becomes clear that building upon our knowledge of GBAF and BAF complex function will be essential for advancements in both mammalian reproductive applications and the development of more effective therapeutic interventions and strategies. Here, we review the roles of the SWI/SNF chromatin remodeling subcomplex GBAF and its subunits in mammalian development and disease.

scholarly journals Molecular Mechanisms of Heat Shock Factors in Cancer

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1202
Author(s):  
Mikael Christer Puustinen ◽  
Lea Sistonen
Keyword(s):  
Heat Shock ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Heat Shock Factors ◽  
Therapeutic Approaches ◽  
The Past ◽  
Cancer Types ◽  
Cellular Pathways ◽  
As Stress ◽  
Regulatory Functions

Malignant transformation is accompanied by alterations in the key cellular pathways that regulate development, metabolism, proliferation and motility as well as stress resilience. The members of the transcription factor family, called heat shock factors (HSFs), have been shown to play important roles in all of these biological processes, and in the past decade it has become evident that their activities are rewired during tumorigenesis. This review focuses on the expression patterns and functions of HSF1, HSF2, and HSF4 in specific cancer types, highlighting the mechanisms by which the regulatory functions of these transcription factors are modulated. Recently developed therapeutic approaches that target HSFs are also discussed.

Quantitative assay and disappearance rate of circulating renin

1964 ◽  
Vol 206 (6) ◽  
pp. 1361-1364 ◽  
Author(s):  
G. Schaechtelin ◽  
D. Regoli ◽  
F. Gross
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Response ◽  
Pressure Response ◽  
Pressure Increase ◽  
Disappearance Rate ◽  
Hypertensive Rats ◽  
Contralateral Kidney ◽  
Blood Pressure Increase ◽  
Hypertensive Animal ◽  
Renal Hypertensive Rats

In isovolemic cross-circulation experiments, a nephrectomized donor rat, into which various doses of hog renin were injected, was connected to a nephrectomized indicator rat. The blood pressure increase thus produced in the indicator rat was compared with the blood pressure response obtained during cross circulation using either intact normotensive or renal hypertensive rats as donor animals. An exponential dose-response relationship was found between hog renin injected into a nephrectomized donor and the blood pressure increase of the indicator rat. Using the cross-circulation technique, the disappearance rate of endogenous reninlike material in the blood of donor animals and of exogenous renin injected into nephrectomized donor animals was examined. If an intact normotensive animal or a unilaterally nephrectomized hypertensive animal is totally nephrectomized, reninlike material disappears from the blood within 1 hr. In renal hypertensive rats with an untouched contralateral kidney which have a higher concentration of reninlike material in the blood, it takes about twice the normal time until reninlike material disappears from the blood after nephrectomy. The increased and prolonged blood pressure response of the nephrectomized animal to renin is not connected with a prolonged persistence of renin in the blood.

scholarly journals Chromatin remodeler Ino80C acts independently of H2A.Z to evict promoter nucleosomes and stimulate transcription of highly expressed genes in yeast

2020 ◽  
Vol 48 (15) ◽  
pp. 8408-8430 ◽  
Author(s):  
Hongfang Qiu ◽  
Emily Biernat ◽  
Chhabi K Govind ◽  
Yashpal Rawal ◽  
Răzvan V Chereji ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Histone Variant ◽  
Yeast Genome ◽  
Chromatin Remodeler ◽  
Chromatin Remodelers ◽  
Highly Expressed Genes ◽  
Induced Genes ◽  
Yeast Genes

Abstract The chromatin remodelers SWI/SNF and RSC function in evicting promoter nucleosomes at highly expressed yeast genes, particularly those activated by transcription factor Gcn4. Ino80 remodeling complex (Ino80C) can establish nucleosome-depleted regions (NDRs) in reconstituted chromatin, and was implicated in removing histone variant H2A.Z from the −1 and +1 nucleosomes flanking NDRs; however, Ino80C’s function in transcriptional activation in vivo is not well understood. Analyzing the cohort of Gcn4-induced genes in ino80Δ mutants has uncovered a role for Ino80C on par with SWI/SNF in evicting promoter nucleosomes and transcriptional activation. Compared to SWI/SNF, Ino80C generally functions over a wider region, spanning the −1 and +1 nucleosomes, NDR and proximal genic nucleosomes, at genes highly dependent on its function. Defects in nucleosome eviction in ino80Δ cells are frequently accompanied by reduced promoter occupancies of TBP, and diminished transcription; and Ino80 is enriched at genes requiring its remodeler activity. Importantly, nuclear depletion of Ino80 impairs promoter nucleosome eviction even in a mutant lacking H2A.Z. Thus, Ino80C acts widely in the yeast genome together with RSC and SWI/SNF in evicting promoter nucleosomes and enhancing transcription, all in a manner at least partly independent of H2A.Z editing.

Functional diversity of ISWI complexes

2004 ◽  
Vol 82 (4) ◽  
pp. 482-489 ◽  
Author(s):  
Sara S Dirscherl ◽  
Jocelyn E Krebs
Keyword(s):  
Chromatin Remodeling ◽  
Catalytic Core ◽  
Chromatin Remodelers ◽  
Form And Function ◽  
Curr Opin Cell Biol ◽  
Chromatid Cohesion ◽  
Chromatin Remodeling Complexes ◽  
And Function ◽  
Diverse Groups ◽  
Nuclear Processes

The yeast SWI/SNF ATP-dependent chromatin remodeling complex was first identified and characterized over 10 years ago (F. Winston and M. Carlson. 1992. Trends Genet. 8: 387–391.) Since then, the number of distinct ATP-dependent chromatin remodeling complexes and the variety of roles they play in nuclear processes have become dizzying (J.A. Martens and F. Winston. 2003. Curr. Opin. Genet. Dev. 13: 136–142; A. Vacquero et al. 2003. Sci. Aging Knowledge Environ. 2003: RE4) — and that does not even include the companion suite of histone modifying enzymes, which exhibit a comparable diversity in both number of complexes and variety of functions (M.J. Carrozza et al. 2003. Trends Genet. 19: 321–329; W. Fischle et al. 2003. Curr. Opin. Cell Biol. 15: 172–183; M. Iizuka and M.M. Smith. 2003. Curr. Opin. Genet. Dev. 13: 1529–1539). This vast complexity is hardly surprising, given that all nuclear processes that involve DNA — transcription, replication, repair, recombination, sister chromatid cohesion, etc. — must all occur in the context of chromatin. The SWI/SNF-related ATP-dependent remodelers are divided into a number of subfamilies, all related by the SWI2/SNF2 ATPase at their catalytic core. In nearly every species where researchers have looked for them, one or more members of each subfamily have been identified. Even the budding yeast, with its comparatively small genome, contains eight different chromatin remodelers in five different subfamilies. This review will focus on just one subfamily, the Imitation Switch (ISWI) family, which is proving to be one of the most diverse groups of chromatin remodelers in both form and function.

scholarly journals bromodomain-containing protein Ibd1 links multiple chromatin-related protein complexes to highly expressed genes in Tetrahymena thermophila

2021 ◽  
Author(s):  
Alejandro Saettone ◽  
Jyoti Garg ◽  
Jean-Philippe Lambert ◽  
Syed Nabeel-Shah ◽  
Marcelo Ponce ◽  
...  
Keyword(s):  
Tetrahymena Thermophila ◽  
Protein Complexes ◽  
Affinity Purification ◽  
Regulation Of Gene Expression ◽  
Methyl Transferase ◽  
Chromatin Remodelers ◽  
Highly Expressed Genes ◽  
Chromatin Remodeling Complexes ◽  
Additional Protein ◽  
Active Transcription

Background The chromatin remodelers of the SWI/SNF family are critical transcriptional regulators. Recognition of lysine acetylation through a bromodomain (BRD) component is key to SWI/SNF function; in most eukaryotes, this function is attributed to SNF2/Brg1. Results Using affinity purification coupled to mass spectrometry (AP–MS) we identified members of a SWI/SNF complex (SWI/SNFTt) in Tetrahymena thermophila. SWI/SNFTt is composed of 11 proteins, Snf5Tt, Swi1Tt, Swi3Tt, Snf12Tt, Brg1Tt, two proteins with potential chromatin-interacting domains and four proteins without orthologs to SWI/SNF proteins in yeast or mammals. SWI/SNFTt subunits localize exclusively to the transcriptionally active macronucleus during growth and development, consistent with a role in transcription. While Tetrahymena Brg1 does not contain a BRD, our AP–MS results identified a BRD-containing SWI/SNFTt component, Ibd1 that associates with SWI/SNFTt during growth but not development. AP–MS analysis of epitope-tagged Ibd1 revealed it to be a subunit of several additional protein complexes, including putative SWRTt, and SAGATt complexes as well as a putative H3K4-specific histone methyl transferase complex. Recombinant Ibd1 recognizes acetyl-lysine marks on histones correlated with active transcription. Consistent with our AP–MS and histone array data suggesting a role in regulation of gene expression, ChIP-Seq analysis of Ibd1 indicated that it primarily binds near promoters and within gene bodies of highly expressed genes during growth. Conclusions Our results suggest that through recognizing specific histones marks, Ibd1 targets active chromatin regions of highly expressed genes in Tetrahymena where it subsequently might coordinate the recruitment of several chromatin-remodeling complexes to regulate the transcriptional landscape of vegetatively growing Tetrahymena cells.

scholarly journals CHD7 interacts with the nucleosome acidic patch for its efficient activity via its N-terminal region

2020 ◽  
Author(s):  
Eunhye Lee ◽  
Chanshin Kang ◽  
Pasi Purhonen ◽  
Hans Hebert ◽  
Karim Bouazoune ◽  
...  
Keyword(s):  
Single Molecule ◽  
Developmental Disorders ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Charge Syndrome ◽  
Terminal Region ◽  
Open Chromatin ◽  
Chromatin Remodeler ◽  
Nucleosome Remodeling ◽  
Chromatin Remodelers

AbstractChromodomain-Helicase DNA binding protein 7 (CHD7) is an ATP dependent chromatin remodeler involved in maintaining open chromatin structure. Mutations of CHD7 gene causes multiple developmental disorders, notably CHARGE syndrome. However, there is not much known about the molecular mechanism by which CHD7 remodels nucleosomes. Here, we performed integrative biophysical analysis on CHD7 chromatin remodeler using crosslinking-mass spectrometry (XL-MS), cryo-Electron Microscopy (cryo-EM) and single-molecule Förster Resonance Energy Transfer (smFRET). We uncover that N-terminal to the Chromodomain (N-CRD) interacts with nucleosome. Importantly, this region is required for efficient ATPase stimulation and nucleosome remodeling activity of CHD7. The cryo-EM analysis on the N-CRD_Chromodomain bound to nucleosome reveals that the N-CRD interacts with the acidic patch of nucleosome. Furthermore, smFRET analysis shows the mutations in the N-CRD result in slow or highly-fluctuating remodeling activity. Collectively, our results uncover the functional importance of a previously unidentified N-terminal region in CHD7 and implicate that the multiple domains in chromatin remodelers are involved in regulating their activities.

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