Cohesin: a regulator of genome integrity and gene expression

Feeney, Katherine M; Wasson, Christopher W.; Parish, Joanna L

doi:10.1042/bj20100151

Cited by 30 publications

(19 citation statements)

References 186 publications

(201 reference statements)

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“…1H) cohesin is bound in the labile mode at that site. This suggests that the nucleolus may act as a reservoir of cohesin that may be important in the event of a DNA DSB or in the regulation of gene expression (19).…”

Section: Discussionmentioning

confidence: 99%

Psm3 Acetylation on Conserved Lysine Residues Is Dispensable for Viability in Fission Yeast but Contributes to Eso1-Mediated Sister Chromatid Cohesion by Antagonizing Wpl1

Feytout

Vaur

Genier

et al. 2011

Molecular and Cellular Biology

107

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In budding yeast and humans, cohesion establishment during S phase requires the acetyltransferase Eco1/Esco1-2, which acetylates the cohesin subunit Smc3 on two conserved lysine residues. Whether Smc3 is the sole Eco1/Esco1-2 effector and how Smc3 acetylation promotes cohesion are unknown. In fission yeast (Schizosaccharomyces pombe), as in humans, cohesin binding to G 1 chromosomes is dynamic and the unloading reaction is stimulated by Wpl1 (human ortholog, Wapl). During S phase, a subpopulation of cohesin becomes stably bound to chromatin in an Eso1 (fission yeast Eco1/Esco1-2)-dependent manner. Cohesin stabilization occurs unevenly along chromosomes. Cohesin remains largely labile at the rDNA repeats but binds mostly in the stable mode to pericentromere regions. This pattern is largely unchanged in eso1⌬ wpl1⌬ cells, and cohesion is unaffected, indicating that the main Eso1 role is counteracting Wpl1. A mutant of Psm3 (fission yeast Smc3) that mimics its acetylated state renders cohesin less sensitive to Wpl1-dependent unloading and partially bypasses the Eso1 requirement but cannot generate the stable mode of cohesin binding in the absence of Eso1. Conversely, nonacetylatable Psm3 reduces the stable cohesin fraction and affects cohesion in a Wpl1-dependent manner, but cells are viable. We propose that Psm3 acetylation contributes to Eso1 counteracting of Wpl1 to secure stable cohesin interaction with postreplicative chromosomes but that it is not the sole molecular event by which this occurs.Following DNA replication in S phase, sister DNA molecules are linked together by cohesin. Thereafter, cohesion between sister chromatids persists throughout the G 2 phase and until mitosis, where it allows chromosome biorientation on the mitotic spindle (16). Defects in this process have been linked to aneuploidy and tumor progression. Cohesin is a multisubunit protein complex made of a dimer of long, flexible Smc subunits, which form a ring-shaped structure stabilized by the binding of a kleisin subunit (Scc1/Rad21 in the mitotic cycle; Rec8 in meiosis) (2, 25). Kleisin cleavage by separase destroys the ring and allows chromatid separation at anaphase (28,43,58). The ring shape of the complex suggested that cohesin ensures cohesion by topological trapping of sister DNA molecules, and strong experimental evidence supports this model (24), although other modes of cohesin-DNA interaction might coexist (29,40).One key aspect of the cohesion cycle is how cohesion is made during S phase. Cohesin is first deposited on unreplicated chromosomes in a reaction requiring ATP hydrolysis by the Smc heads and the cohesin-loading complex Scc2/Scc4 (4,5,15,61). In an unperturbed cell cycle, cohesion is made exclusively during S phase, and except in the event of a DNA double-strand break (DSB), cohesin loading after DNA replication does not result in functional cohesion (26,34,51,60). Numerous studies have shown that mutations in nonessential factors associated with the replication fork machinery affect sister chromatid cohesion, leadin...

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Section: Discussionmentioning

confidence: 99%

Psm3 Acetylation on Conserved Lysine Residues Is Dispensable for Viability in Fission Yeast but Contributes to Eso1-Mediated Sister Chromatid Cohesion by Antagonizing Wpl1

Feytout

Vaur

Genier

et al. 2011

Molecular and Cellular Biology

107

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“…Transient decay and proteolysis of meiotic cohesins during a long arrest-phase could contribute to precocious chiasma resolution when cohesins do not become replaced, and thus susceptibility to random segregation may become increased in functional univalents once oocytes resume maturation [20,21]. In addition, the loss of cohesion proteins might affect chromatin conformation and gene expression in the aged oocyte [22] and thus contribute to aberrations in the normal expression patterns that are required to control chromosome segregation and oocyte quality. A summary of these events is shown in Figure 1(B).…”

Section: Dictyate Stage Arrestmentioning

confidence: 97%

“…In Figure 1 Stages of oogenesis that are susceptible to disturbances and events leading synergistically to high risks for errors in chromosome segregation in oocytes at advanced maternal age (A) Events in the embryonic ovary, including presence of trisomic cell line of oogonia [10], failure to recombine and/or numbers and placement of exchanges on homologous chromosomes [8,[11][12][13]. (B) Events during long meiotic arrest of dictyate stage-arrested oocyte in the primordial follicle post-birth, including accumulation of insult by environment, life style/nutrition and ROS, loss of cohesion during chronological ageing and reduction of follicle pool (physiological ageing) by continuous recruitment and atresia of follicles [5][6][7][16][17][18][19][20][21][22]. (C) Pre-ovulatory events in the growing oocyte or after resumption of maturation by changes in follicular development, oxygen supply and synthesis/degradation of RNAs and cell-cell signalling, causing changes in gene expression and proteins affecting spindle formation, cell-cycle control and sequential chromosome segregation [25,26,[28][29][30][31][32][33], including activity and distribution of MCAK (D).…”

Section: Introductionmentioning

confidence: 99%

Chromosomal and cytoplasmic context determines predisposition to maternal age-related aneuploidy: brief overview and update on MCAK in mammalian oocytes

Eichenlaub-Ritter

Staubach

Trapphoff

2010

Biochemical Society Transactions

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It has been known for more than half a century that the risk of conceiving a child with trisomy increases with advanced maternal age. However, the origin of the high susceptibility to nondisjunction of whole chromosomes and precocious separation of sister chromatids, leading to aneuploidy in aged oocytes and embryos derived from them, cannot be traced back to a single disturbance and mechanism. Instead, analysis of recombination patterns of meiotic chromosomes of spread oocytes from embryonal ovary, and of origins and exchange patterns of extra chromosomes in trisomies, as well as morphological and molecular studies of oocytes and somatic cells from young and aged females, show chromosome-specific risk patterns and cellular aberrations related to the chronological age of the female. In addition, analysis of the function of meiotic- and cell-cycle-regulating genes in oogenesis, and the study of the spindle and chromosomal status of maturing oocytes, suggest that several events contribute synergistically to errors in chromosome segregation in aged oocytes in a chromosome-specific fashion. For instance, loss of cohesion may differentially predispose chromosomes with distal or pericentromeric chiasmata to nondisjunction. Studies on expression in young and aged oocytes from human or model organisms, like the mouse, indicate that the presence and functionality/activity of gene products involved in cell-cycle regulation, spindle formation and organelle integrity may be altered in aged oocytes, thus contributing to a high risk of error in chromosome segregation in meiosis I and II. Genes that are often altered in aged mouse oocytes include MCAK (mitotic-centromere-associated protein), a microtubule depolymerase, and AURKB (Aurora kinase B), a protein of the chromosomal passenger complex that has many targets and can also phosphorylate and regulate MCAK localization and activity. Therefore we explored the role of MCAK in maturing mouse oocytes by immunofluorescence, overexpression of a MCAK-EGFP (enhanced green fluorescent protein) fusion protein, knockdown of MCAK by RNAi (RNA interference) and inhibition of AURKB. The observations suggest that MCAK is involved in spindle regulation, chromosome congression and cell-cycle control, and that reductions in mRNA and protein in a context of permissive SAC (spindle assembly checkpoint) predispose to aneuploidy. Failure to recruit MCAK to centromeres and low expression patterns, as well as disturbances in regulation of enzyme localization and activity, e.g. due to alterations in activity of AURKB, may therefore contribute to maternal age-related rises in aneuploidy in mammalian oocytes.

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“…In addition to its role in sister chromatid cohesion, the cohesin protein complex facilitates several kinds of chromatin interactions, some of which are cell type-specific [7], [8], [9], [10], [11]. Cohesin/CTCF co-localisation also aids transcriptional regulation and insulation [12], [13].…”

Section: Introductionmentioning

confidence: 99%

Stage-Specific Binding Profiles of Cohesin in Resting and Activated B Lymphocytes Suggest a Role for Cohesin in Immunoglobulin Class Switching and Maturation

et al. 2014

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The immunoglobulin heavy chain locus (Igh) features higher-order chromosomal interactions to facilitate stage-specific assembly of the Ig molecule. Cohesin, a ring-like protein complex required for sister chromatid cohesion, shapes chromosome architecture and chromatin interactions important for transcriptional regulation and often acts together with CTCF. Cohesin is likely involved in B cell activation and Ig class switch recombination. Hence, binding profiles of cohesin in resting mature murine splenic B lymphocytes and at two stages after cell activation were elucidated by chromatin immunoprecipitation and deep sequencing. Comparative genomic analysis revealed cohesin extensively changes its binding to transcriptional control elements after 48 h of stimulation with LPS/IL-4. Cohesin was clearly underrepresented at switch regions regardless of their activation status, suggesting that switch regions need to be cohesin-poor. Specific binding changes of cohesin at B-cell specific gene loci Pax5 and Blimp-1 indicate new cohesin-dependent regulatory pathways. Together with conserved cohesin/CTCF sites at the Igh 3′RR, a prominent cohesin/CTCF binding site was revealed near the 3′ end of Cα where PolII localizes to 3′ enhancers. Our study shows that cohesin likely regulates B cell activation and maturation, including Ig class switching.

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Cohesin: a regulator of genome integrity and gene expression

Cited by 30 publications

References 186 publications

Psm3 Acetylation on Conserved Lysine Residues Is Dispensable for Viability in Fission Yeast but Contributes to Eso1-Mediated Sister Chromatid Cohesion by Antagonizing Wpl1

Psm3 Acetylation on Conserved Lysine Residues Is Dispensable for Viability in Fission Yeast but Contributes to Eso1-Mediated Sister Chromatid Cohesion by Antagonizing Wpl1

Chromosomal and cytoplasmic context determines predisposition to maternal age-related aneuploidy: brief overview and update on MCAK in mammalian oocytes

Stage-Specific Binding Profiles of Cohesin in Resting and Activated B Lymphocytes Suggest a Role for Cohesin in Immunoglobulin Class Switching and Maturation

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