Satellite repeat transcripts modulate heterochromatin condensates and safeguard chromosome stability in mouse embryonic stem cells.

Heterochromatin maintains genome integrity and function, and is organised into distinct nuclear domains. Some of these domains are proposed to form by phase separation through the accumulation of HP1ɑ. Mouse heterochromatin contains noncoding major satellite repeats (MSR), which are highly transcribed in mouse embryonic stem cells (ESCs).

A Tale of Two States: Pluripotency Regulation of Telomeres.

Inside the nucleus, chromatin is functionally organized and maintained as a complex three-dimensional network of structures with different accessibility such as compartments, lamina associated domains, and membraneless bodies. Chromatin is epigenetically and transcriptionally regulated by an intricate and dynamic interplay of molecular processes to ensure genome stability. Phase separation, a process that involves the spontaneous organization of a solution into separate phases, has been proposed as a mechanism for the timely coordination of several cellular processes, including replication, transcription and DNA repair.

Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent State Transition.

Transcriptional enhancers, including super-enhancers (SEs), form physical interactions with promoters to regulate cell-type-specific gene expression. SEs are characterized by high transcription factor occupancy and large domains of active chromatin, and they are commonly assigned to target promoters using computational predictions. How promoter-SE interactions change upon cell state transitions, and whether transcription factors maintain SE interactions, have not been reported.

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline.

Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age-associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale.

The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells.

An open and decondensed chromatin organization is a defining property of pluripotency. Several epigenetic regulators have been implicated in maintaining an open chromatin organization, but how these processes are connected to the pluripotency network is unknown. Here, we identified a new role for the transcription factor NANOG as a key regulator connecting the pluripotency network with constitutive heterochromatin organization in mouse embryonic stem cells.

A new role for histone deacetylase 5 in the maintenance of long telomeres.

Telomeres are major regulators of genome stability and cell proliferation. A detailed understanding of the mechanisms involved in their maintenance is of foremost importance. Of those, telomere chromatin remodeling is probably the least studied; thus, we intended to explore the role of a specific histone deacetylase on telomere maintenance.

HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment.

Telomeres are repetitive DNA structures that, together with the shelterin and the CST complex, protect the ends of chromosomes. Telomere shortening is mitigated in stem and cancer cells through the de novo addition of telomeric repeats by telomerase. Telomere elongation requires the delivery of the telomerase complex to telomeres through a not yet fully understood mechanism.

The heterochromatic chromosome caps in great apes impact telomere metabolism.

In contrast with the limited sequence divergence accumulated after separation of higher primate lineages, marked cytogenetic variation has been associated with the genome evolution in these species. Studying the impact of such structural variations on defined molecular processes can provide valuable insights on how genome structural organization contributes to organismal evolution. Here, we show that telomeres on chromosome arms carrying subtelomeric heterochromatic caps in the chimpanzee, which are completely absent in humans, replicate later than telomeres on chromosome arms without caps.

Telomeres and the nucleus.

Telomeres are crucial for the maintenance of genome stability through "capping" of chromosome ends to prevent their recognition as double-strand breaks, thus avoiding end-to-end fusions or illegitimate recombination [1-3]. Similar to other genomic regions, telomeres participate to the nuclear architecture while being highly mobile. The interaction of telomeres with nuclear domains or compartments greatly differs not only between organisms but also between cells within the same organism.

The role of recombination in telomere length maintenance.

Human telomeres shorten during each cell division, predominantly because of incomplete DNA replication. This eventually results in short uncapped telomeres that elicit a DNA-damage response, leading to cellular senescence. However, evasion of senescence results in continued cell division and telomere erosion ultimately results in genome instability.