A transient ischemic environment induces reversible compaction of chromatin

Abstract

BackgroundCells detect and adapt to hypoxic and nutritional stress through immediate transcriptional, translational and metabolic responses. The environmental effects of ischemia on chromatin nanostructure were investigated using single molecule localization microscopy of DNA binding dyes and of acetylated histones, by the sensitivity of chromatin to digestion with DNAseI, and by fluorescence recovery after photobleaching (FRAP) of core and linker histones.ResultsShort-term oxygen and nutrient deprivation of the cardiomyocyte cell line HL-1 induces a previously undescribed chromatin architecture, consisting of large, chromatin-sparse voids interspersed between DNA-dense hollow helicoid structures 40–700 nm in dimension. The chromatin compaction is reversible, and upon restitution of normoxia and nutrients, chromatin transiently adopts a more open structure than in untreated cells. The compacted state of chromatin reduces transcription, while the open chromatin structure induced upon recovery provokes a transitory increase in transcription. Digestion of chromatin with DNAseI confirms that oxygen and nutrient deprivation induces compaction of chromatin. Chromatin compaction is associated with depletion of ATP and redistribution of the polyamine pool into the nucleus. FRAP demonstrates that core histones are not displaced from compacted chromatin; however, the mobility of linker histone H1 is considerably reduced, to an extent that far exceeds the difference in histone H1 mobility between heterochromatin and euchromatin.ConclusionsThese studies exemplify the dynamic capacity of chromatin architecture to physically respond to environmental conditions, directly link cellular energy status to chromatin compaction and provide insight into the effect ischemia has on the nuclear architecture of cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0802-2) contains supplementary material, which is available to authorized users.

The Spermine Phosphate-Bound Cyclooctaoxygen Sodium Epigenetic Shell of Euchromatin DNA Is Destroyed by the Epigenetic Poison Glyphosate

“…In summary, this reflects the high mitotic chromatin condensation grade and is confirming the results with hypoxia-induced chromatin condensation under coinciding polyamine pool nuclear translocation [4]. Interestingly, spermine and spermidine induced B-DNA to Z-DNA transition at epigenetic, non-5-methylated CpG island hotspots of prokaryotic plasmid DNA (pBR322 derivative) [54], but, in contrast, stabilized and condensed prokaryotic chromosomal B-DNA [55].…”

“…In view of the important findings of Kirmes et al [4] we were not aware of in 2015, that an interaction of eukaryotic chromatin DNA structure with atmospheric oxygen partial pressure takes place, we have to correct now previous postulations [5]. We concluded that the cyclooctaoxygen sodiumbridged spermine phosphate epigenetic shell is confined to both interphase relaxed euchromatin and mitotic condensed chromatin [5].…”

“…We concluded that the cyclooctaoxygen sodiumbridged spermine phosphate epigenetic shell is confined to both interphase relaxed euchromatin and mitotic condensed chromatin [5]. Since, under switching to hypoxic conditions eukaryotic cell chromatin gets highly condensed [4], accompanied by redistribution of the polyamine pool to the nucleus [4], the cyclooctaoxygen sodium-bridged spermine phosphate epigenetic shell can only be restricted to actively transcribed gene regions of eukaryotic 'open' euchromatin, excluding occupation of condensed chromatin. Hypoxia should largely prevent metabolic formation of cyclooctaoxygen.…”

The Spermine Phosphate-Bound Cyclooctaoxygen Sodium Epigenetic Shell of Euchromatin DNA is Destroyed by the Epigenetic Poison Glyphosate

“…The following materials were utilized: NC (C9H14ClN3O5 × 2 ClNaO8 × 2 H2O × ½ C3H6O) = [tetrakis(β-D-cytidin-N 3 -ium)(octoxocane-κ 4 …”

“…In 1990 a ninth allotropic modification of oxygen was theoretically predicted [10], the cyclooctaoxygen (cyclo-O8, octoxocane) ( Figure 2A) [8,10], assumed to exist in analogy to the common modification of elemental sulfur, cyclooctasulfur (cyclo-S8, octathiocane) [10]. Our group reported [5] the (biomimetic) synthesis, isolation, chemical characterization, biochemical and epigenetic significance of cyclo-O8 in form of its sodium crown complex, (octoxocane-κ 4 O 1 ,O 3 ,O 5 ,O 7 )sodium(1+) or cyclo-O8-Na + ( Figure 2B) [5].…”