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1.
Mol Cell ; 79(6): 881-901, 2020 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-32768408

RESUMEN

Nucleosomes package genomic DNA into chromatin. By regulating DNA access for transcription, replication, DNA repair, and epigenetic modification, chromatin forms the nexus of most nuclear processes. In addition, dynamic organization of chromatin underlies both regulation of gene expression and evolution of chromosomes into individualized sister objects, which can segregate cleanly to different daughter cells at anaphase. This collaborative review shines a spotlight on technologies that will be crucial to interrogate key questions in chromatin and chromosome biology including state-of-the-art microscopy techniques, tools to physically manipulate chromatin, single-cell methods to measure chromatin accessibility, computational imaging with neural networks and analytical tools to interpret chromatin structure and dynamics. In addition, this review provides perspectives on how these tools can be applied to specific research fields such as genome stability and developmental biology and to test concepts such as phase separation of chromatin.


Asunto(s)
Cromatina/genética , Cromosomas/genética , ADN/genética , Nucleosomas/genética , Reparación del ADN/genética , Replicación del ADN/genética , Epigénesis Genética/genética , Humanos
2.
FASEB J ; 38(13): e23741, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38896550

RESUMEN

Access to scientific meetings and conferences is limited in low- and middle-income countries (LMIC). Efforts are being implemented to rectify this issue through short workshops, seminars, and conferences. Sena Institute of Technology (SIT), a nonprofit research institute based in Ghana, is one such organization championing this initiative. Through a partnership with the Federation of American Societies for Experimental Biology (FASEB), SIT hosted the first FASEB conference in Africa from August 27-30, 2023 in Ghana. The 3-day conference brought together scientists specialized in imaging, genetics, and cell biology from across the globe to discuss the theme "Imaging Cellular and Chromosome Dynamics." The Ghanaian Ministry of Environment, Science, Technology and Innovation (MESTI) and the Ghana Tourism Authority (GTA) provided local support to the meeting. At the end of the conference, participants recommended continuing engagement and the organization of more such meetings on the African continent.


Asunto(s)
Cromosomas , Humanos , Ghana , Congresos como Asunto
4.
PLoS Genet ; 8(8): e1002845, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22916023

RESUMEN

Gyrase catalyzes negative supercoiling of DNA in an ATP-dependent reaction that helps condense bacterial chromosomes into a compact interwound "nucleoid." The supercoil density (σ) of prokaryotic DNA occurs in two forms. Diffusible supercoil density (σ(D)) moves freely around the chromosome in 10 kb domains, and constrained supercoil density (σ(C)) results from binding abundant proteins that bend, loop, or unwind DNA at many sites. Diffusible and constrained supercoils contribute roughly equally to the total in vivo negative supercoil density of WT cells, so σ = σ(C)+σ(D). Unexpectedly, Escherichia coli chromosomes have a 15% higher level of σ compared to Salmonella enterica. To decipher critical mechanisms that can change diffusible supercoil density of chromosomes, we analyzed strains of Salmonella using a 9 kb "supercoil sensor" inserted at ten positions around the genome. The sensor contains a complete Lac operon flanked by directly repeated resolvase binding sites, and the sensor can monitor both supercoil density and transcription elongation rates in WT and mutant strains. RNA transcription caused (-) supercoiling to increase upstream and decrease downstream of highly expressed genes. Excess upstream supercoiling was relaxed by Topo I, and gyrase replenished downstream supercoil losses to maintain an equilibrium state. Strains with TS gyrase mutations growing at permissive temperature exhibited significant supercoil losses varying from 30% of WT levels to a total loss of σ(D) at most chromosome locations. Supercoil losses were influenced by transcription because addition of rifampicin (Rif) caused supercoil density to rebound throughout the chromosome. Gyrase mutants that caused dramatic supercoil losses also reduced the transcription elongation rates throughout the genome. The observed link between RNA polymerase elongation speed and gyrase turnover suggests that bacteria with fast growth rates may generate higher supercoil densities than slow growing species.


Asunto(s)
Cromosomas Bacterianos , Girasa de ADN/genética , ADN Bacteriano/genética , ADN Superhelicoidal/genética , Escherichia coli/genética , Salmonella typhimurium/genética , Elongación de la Transcripción Genética , Sitios de Unión , Girasa de ADN/metabolismo , ADN Bacteriano/química , ADN Superhelicoidal/química , ARN Polimerasas Dirigidas por ADN/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Regulación Bacteriana de la Expresión Génica , Genes Reporteros , Operón Lac , Mutación , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Unión Proteica , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Recombinasas/genética , Recombinasas/metabolismo , Rifampin/farmacología , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/enzimología , Elongación de la Transcripción Genética/efectos de los fármacos
5.
Front Pharmacol ; 13: 1045783, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36703761

RESUMEN

Leiomyomas, or uterine fibroids as they are commonly known, are mostly seen in women of reproductive age. However, they can go undetected in most women, and approximately 25% of women show clinical symptoms. Although fibroids are a global burden impacting 80% of premenopausal women, they are more prevalent among Black women than among women of other races. Based on clinical diagnosis, the estimated cumulative incidence of fibroids in women ≤50 years old is significantly higher for black (>80%) versus white women (∼70%). The cause of leiomyomas is not clearly known, but studies have shown evidence of factors that drive the development or exacerbation of the disease. Evidence has linked risk factors such as lifestyle, age, environment, family history of uterine fibroids, and vitamin D deficiencies to an increased risk of uterine fibroids, which impact women of African descent at higher rates. Treatments may be invasive, such as hysterectomy and myomectomy, or non-invasive, such as hormonal or non-hormonal therapies. These treatments are costly and tend to burden women who have the disease. Sub-Saharan Africa is known to have the largest population of black women, yet the majority of uterine fibroid studies do not include populations from the continent. Furthermore, the prevalence of the disease on the continent is not well determined. To effectively treat the disease, its drivers need to be understood, especially with regard to racial preferences. This paper aims to review the existing literature and build a case for conducting future research on African women.

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