Chromatin
Dotaz
Zobrazit nápovědu
elektronický časopis
- Konspekt
- Obecná genetika. Obecná cytogenetika. Evoluce
- NLK Obory
- genetika, lékařská genetika
- NLK Publikační typ
- elektronické časopisy
Methods in enzymology ; Vol. 304
[1st ed.] xxxiv, 815 s. : ill.
This Special Issue highlights the advantages of using combined approaches to explore chromatin molecular complexes [...].
- MeSH
- chromatin * genetika MeSH
- genom * MeSH
- restrukturace chromatinu MeSH
- Publikační typ
- úvodníky MeSH
Smarca5, an ATPase of the ISWI class of chromatin remodelers, is a key regulator of chromatin structure, cell cycle and DNA repair. Smarca5 is deregulated in leukemia and breast, lung and gastric cancers. However, its role in oncogenesis is not well understood. Chromatin remodelers often play dosage-dependent roles in cancer. We therefore investigated the epigenomic and phenotypic impact of controlled stepwise attenuation of Smarca5 function in the context of primary cell transformation, a process relevant to tumor formation. Upon conditional single- or double-allele Smarca5 deletion, the cells underwent both accelerated growth arrest and senescence entry and displayed gradually increased sensitivity to genotoxic insults. These phenotypic characteristics were explained by specific remodeling of the chromatin structure and the transcriptome in primary cells prior to the immortalization onset. These molecular programs implicated Smarca5 requirement in DNA damage repair, telomere maintenance, cell cycle progression and in restricting apoptosis and cellular senescence. Consistent with the molecular programs, we demonstrate for the first time that Smarca5-deficient primary cells exhibit dramatically decreased capacity to bypass senescence and immortalize, an indispensable step during cell transformation and cancer development. Thus, Smarca5 plays a crucial role in key homeostatic processes and sustains cancer-promoting molecular programs and cellular phenotypes.
OBJECTIVES: The frequency of aneuploidies in human oocytes is extremely high. It is hypothesized that the cause may be due to abnormal chromatin (histone) acetylation/deacetylation. The aim of our study was to analyzed the acetylation/deacetylation pattern in spare human oocytes. MATERIALS AND METHODS: Human spare oocytes (311), in other words oocytes that were not mature when collected from follicles or control oocytes (bovine, mouse), were fixed with paraformaldehyde and then labeled with antibodies against acetylated histones. RESULTS: Labeling against AcH4/K12 or hyperacetylated H4 showed high intensity of the fluorescence signal in all immature (germinal vesicle staged) and approximately 50% of the maturing (mature) oocytes. CONCLUSION: In conclusion, the labeling of human oocytes (chromosomes) showed very inconsistent patterns of acetylation/deacetylation, what may suggest they did not reach the metaphase II stage at the time of follicle aspiration, and were epigenetically abnormal. It may also explain the high frequency of chromosomal abnormalities in human oocytes.
- MeSH
- acetylace MeSH
- chromatin metabolismus MeSH
- histonacetyltransferasy metabolismus MeSH
- histondeacetylasy metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- metafáze MeSH
- myši MeSH
- oocyty cytologie metabolismus MeSH
- posttranslační úpravy proteinů MeSH
- restrukturace chromatinu MeSH
- skot MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- skot MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
