Untersuchungen von menschlichen Zellen mit ungewöhnlicher Chromatin-Anordnung und Zellkernform

Extensive changes of higher order chromatin arrangements can be
observed during prometaphase, terminal cell differentiation and
cellular senescence. Experimental systems where major
reorganization of nuclear architecture can be induced under defined
conditions, may help to better understand the functional
implications of such changes. Here, we report on profound chromatin
reorganization in fibroblast nuclei by chaetocin, a
thiodioxopiperazine metabolite. Chaetocin induces strong
condensation of chromosome territories separated by a wide
interchromatin space largely void of DNA. Cell viability is
maintained irrespective of this peculiar chromatin phenotype. Cell
cycle markers, histone signatures, and tests for cellular
senescence and for oxidative stress indicate that chaetocin induced
chromatin condensation/clustering (CICC) represents a distinct
entity among nuclear phenotypes associated with condensed
chromatin. The territorial organization of entire chromosomes is
maintained in CICC nuclei; however, the conventional nuclear
architecture harboring gene-dense chromatin in the nuclear interior
and gene-poor chromatin at the nuclear periphery is lost. Instead
gene-dense and transcriptionally active chromatin is shifted to the
periphery of individual condensed chromosome territories where
nascent RNA becomes highly enriched around their outer surface.
This chromatin reorganization makes CICC nuclei an attractive model
system to study this border zone as a distinct compartment for
transcription. Induction of CICC is fully inhibited by
thiol-dependent antioxidants, but is not related to the production
of reactive oxygen species. Our results suggest that chaetocin
functionally impairs the thioredoxin (Trx) system, which is
essential for deoxynucleotide synthesis, but in addition involved
in a wide range of cellular functions. The mechanisms involved in
CICC formation remain to be fully explored