Cell cycle regulated transcription of heterochromatin in mammals vs. fission yeast: Functional conservation or coincidence?

Abstract

Although it is tempting to speculate that the transcription-dependent heterochromatin assembly pathway found in fission yeast may operate in higher mammals, transcription of heterochromatin has been difficult to substantiate in mammalian cells. We recently demonstrated that transcription from the mouse pericentric heterochromatin major (gamma) satellite repeats is under cell cycle control, being sharply downregulated at the metaphase to anaphase transition and resuming in late G(1)-phase dependent upon passage through the restriction point. The highest rates of transcription were in early S-phase and again in mitosis with different RNA products detected at each of these times.(1) Importantly, differences in the percentage of cells in G(1)-phase can account for past discrepancies in the detection of major satellite transcripts and suggest that pericentric heterochromatin transcription takes place in all proliferating mammalian cells. A similar cell cycle regulation of heterochromatin transcription has now been shown in fission yeast,(2,3) providing further support for a conserved mechanism. However, there are still fundamental differences between these two systems that preclude the identification of a functional or mechanistic link.

Epigenetic modifications in sex heterochromatin of vole rodents

“…Finally, we analyzed if the transcription levels of pMAHae2, pMA11/3, and LINE-1 sequences are altered during mitotic arrest, since cell proliferation seems to be an important factor regulating the transcription of heterochromatic sequences in some species (Lu and Gilbert 2008). We performed a relative comparison by qRT-PCR method using the cellular pools described above, which were differentially enriched in mitotic cells by colcemid arrest.…”

Chromosome segregation and organization are targets of 5′-Fluorouracil in eukaryotic cells

“…An apparent paradox is that the transcription of heterochromatin is a key to its silencing, but heterochromatin actually functions as a dynamic structure whose expression is cell cycle regulated from yeast to mammalian cells. 49,50 Despite its silent state throughout most of the cell cycle, the partial disruption of heterochromatin structure during S phase enables the transcription machinery to access these regions leading to the expression of centromeric repeats in S. pombe. 51 Thus, the decreased levels of dg and dh transcripts might be a consequence of the delayed entry into S phase detected in 5FU-treated cells.…”

Mechanisms of epigenetic inheritance: Copying of Polycomb repressed chromatin

“…[42][43][44][45] Many of the same proteins and histone modifications are involved in maintenance of mammalian heterochromatin suggesting the mechanisms may be conserved. 46 Recently, cell cycle regulated, non-coding RNA transcripts from heterochromatin regions were detected in early S-phase in mammalian cells, 47,48 before the replication of heterochromatin; their role in duplicating the chromatin structure is not yet clear.…”