In the fission yeast Schizosaccharomyces pombe, the RNAi pathway plays an important role in the formation and maintenance of heterochromatin Heterochromatin, or silent chromatin, is an epigenetically inherited attribute of eukaryotic chromosomes which is required for gene regulation, chromosome segregation and maintenance of genome stability In S pombe, heterochromatin forms on related repetitive DNA sequences at specific loci These repetitive sequences, in concert with the RNAi machinery, are thought to attract several proteins including chromatin-modifying enzymes which act to promote heterochromatin formation The purification of complexes participating in heterochromatin formation has allowed us to begin to analyse in detail the processes involved In the future this will help us to understand how the RNAi machinery acts to induce the chromatin modifications which lead to heterochromatin assembly in fission yeast

RNAi-mediated chromatin silencing in fission yeast.

Eukaryotic DNA is organized into structurally distinct domains that regulate gene expression and chromosome behavior. Epigenetically heritable domains of heterochromatin control the structure and expression of large chromosome domains and are required for proper chromosome segregation. Recent studies have identified many of the enzymes and structural proteins that work together to assemble heterochromatin. The assembly process appears to occur in a stepwise manner involving sequential rounds of histone modification by silencing complexes that spread along the chromatin fiber by self-oligomerization, as well as by association with specifically modified histone amino-terminal tails. Finally, an unexpected role for noncoding RNAs and RNA interference in the formation of epigenetic chromatin domains has been uncovered.

https://science.sciencemag.org/content/sci/301/5634/798.full.pdf

Heterochromatin and Epigenetic Control of Gene Expression

/pdf/heterochromatin-revisited-nat-rev-genet-1s49kjmsfl.pdf

Heterochromatin revisited. Nat Rev Genet

The cohesin complex is a major constituent of interphase and mitotic chromosomes. Apart from its role in mediating sister chromatid cohesion, it is also important for DNA double-strand-break repair and transcriptional control. The functions of cohesin are regulated by phosphorylation, acetylation, ATP hydrolysis, and site-specific proteolysis. Recent evidence suggests that cohesin acts as a novel topological device that traps chromosomal DNA within a large tripartite ring formed by its core subunits.

Cohesin: Its Roles and Mechanisms

http://regulatorygenomicsgroup.org/resources/parelho_hadjur_cell2008.pdf

Cohesins Functionally Associate with CTCF on Mammalian Chromosome Arms

Fission yeast centromeres, like those of higher eukaryotes, are composed of repeated DNA structures and associated heterochromatin protein complexes, that have a critical function in the faithful segregation of chromosomes during cell division. Cohesin protein complexes, which are essential for sister-chromatid cohesion and proper chromosome segregation, are enriched at centromeric repeats. We have identified a functional and physical link between heterochromatin and cohesin. We find that the preferential localization of cohesins at the centromeric repeats is dependent on Swi6, a conserved heterochromatin protein that is required for proper kinetochore function. Cohesin is also enriched at the mating-type heterochromatic region in a manner that depends on Swi6 and is required to preserve the genomic integrity of this locus. We provide evidence that a cohesin subunit Psc3 interacts with Swi6 and its mouse homologue HP1. These data define a conserved function of Swi6/HP1 in recruitment of cohesin to heterochromatic regions, promoting the proper segregation of chromosomes.

Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast

The post-translational modifications of histones are key to the modulation of chromatin structure. Distinct patterns of modifications established by histone-modifying enzymes control diverse chromosomal processes. Here, we report the purification and molecular characterization of the fission yeast Clr6 histone deacetyl ase involved in higher order chromatin assembly. We show that a chromodomain protein Alp13, which belongs to the conserved MRG protein family linked to cellular senescence in humans, is associated with Clr6. In addition, Clr6 interacts with homologs of the mammalian transcriptional co-repressors Sin3, Pst1 and Pst2, and a WD40 repeat-containing protein, Prw1. Alp13, Pst2 and Prw1 form a stable complex with Clr6 in the nucleus. Deletion of any of these factors causes progressive loss of viability and sensitivity to DNA-damaging agents, and impairs condensation/resolution of chromosomes during mitosis. This is accompanied by hyperacetylation of histones and a reduction in histone H3 Ser10 phosphorylation, which correlates with chromosome condensation during mitosis. These results link the MRG family protein Alp13 to histone deacetylation, and suggest that Clr6 and its associated factors are essential for fundamental chromosomal events.

/pdf/alp13-an-mrg-family-protein-is-a-component-of-fission-yeast-2ftu11ni1h.pdf

Alp13, an MRG family protein, is a component of fission yeast Clr6 histone deacetylase required for genomic integrity

Uranium is an important nuclear element, and its efficient recovery is of great significance to nuclear industry and to nuclear safety. Herein, we rationally design robust antifouling fiber membranes (Anti-NH2-AO FMs) by facilely grafting two novel ligands on porous surfaces. The efficient ligands, i.e., NH2-AO and GSH, endow the membranes with rapid U-capture rate, good hydrophilicity and antifouling ability. Anti-NH2-AO FMs display porous fiber network structure, good flexibility, and high mechanical strength (9.0 MPa). The uranium capture rate reaches up to 167 mg g−1 h−1 in the first two hours, and they can reduce uranium to 11 ppb in 2 ppm uranium-contaminated water, which is below the drinking water limit. Furthermore, Anti-NH2-AO FMs still exhibit very high seawater permeability (6186 L m−2 h−1 bar−1) and flux recovery ratio (95.12 %) after three seawater fouling cycles. The imaging tests visually demonstrate their antiadhesion to the bacteria. In addition, they have good selectivity and long service life (10 cycles of adsorption-desorption). Kinetics models and XPS analyses illustrate the uranium adsorption mechanisms. Compared with the current membranes and fibers, the Anti-NH2-AO displays the advantages of exceptional properties and easy preparation, and we believe that it possesses great potential in the practical uranium recovery. 

Guoping Xiao

Papers

Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast

Alp13, an MRG family protein, is a component of fission yeast Clr6 histone deacetylase required for genomic integrity

Bioinspired grafting of peptide and NH2-AO to construct antifouling fiber membranes for fast uranium recovery from wastewater and seawater

Directional dendritic gels constructed by binder-regulated freeze casting for enhanced uranium extraction from seawater