Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age

Chatzidaki, Emmanouella E.; Powell, Sean; Dequeker, Bart J H; Gassler, Johanna; Silva, Mariana C.C.; Tachibana, Kikuë

doi:10.1016/j.cub.2021.06.076

Cited by 35 publications

(20 citation statements)

References 90 publications

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“…Although the mechanism of bypassing obstacles is not known, it is conceivable that a topological engagement of proteins around DNA could interfere with cohesin binding to DNA to ‘swing over’ a protein 46 . Consistent with this, cohesin that topologically entraps sister chromatids restricts loop extrusion mediated by other cohesin complexes in oocytes 32 , 47 . In addition, the YDF disordered region alters the outcome of cohesin–MCM collisions from blocking to pausing, which suggests that MCMs are active chemical barriers with binding sites rather than passive physical barriers.…”

Section: Discussionsupporting

confidence: 63%

“…snHi-C was carried out as previously described 27 , 28 , 32 , 47 . Pronuclei of wild-type, Scc1 Δ/Δ , Wapl Δ/Δ and Zp3-dsCTCF zygotes were fixed around 1.5 h after visualization of pronuclei (corresponding to 6–6.5 h after fertilization) and therefore are expected to be in G1 phase of the cell cycle.…”

Section: Methodsmentioning

confidence: 99%

“…snHi-C data were processed and analysed similarly to a previous report 28 and as previously described in 27 , 32 , 47 . In brief, the reads of each sample were mapped to the mm9 genome with bwa and processed by the pairtools framework ( https://pairtools.readthedocs.io/en/latest/ ) into pairs files.…”

Section: Methodsmentioning

confidence: 99%

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MCM complexes are barriers that restrict cohesin-mediated loop extrusion

Dequeker

Scherr

Brandão

et al. 2022

Nature

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Eukaryotic genomes are compacted into loops and topologically associating domains (TADs)1–3, which contribute to transcription, recombination and genomic stability4,5. Cohesin extrudes DNA into loops that are thought to lengthen until CTCF boundaries are encountered6–12. Little is known about whether loop extrusion is impeded by DNA-bound machines. Here we show that the minichromosome maintenance (MCM) complex is a barrier that restricts loop extrusion in G1 phase. Single-nucleus Hi-C (high-resolution chromosome conformation capture) of mouse zygotes reveals that MCM loading reduces CTCF-anchored loops and decreases TAD boundary insulation, which suggests that loop extrusion is impeded before reaching CTCF. This effect extends to HCT116 cells, in which MCMs affect the number of CTCF-anchored loops and gene expression. Simulations suggest that MCMs are abundant, randomly positioned and partially permeable barriers. Single-molecule imaging shows that MCMs are physical barriers that frequently constrain cohesin translocation in vitro. Notably, chimeric yeast MCMs that contain a cohesin-interaction motif from human MCM3 induce cohesin pausing, indicating that MCMs are ‘active’ barriers with binding sites. These findings raise the possibility that cohesin can arrive by loop extrusion at MCMs, which determine the genomic sites at which sister chromatid cohesion is established. On the basis of in vivo, in silico and in vitro data, we conclude that distinct loop extrusion barriers shape the three-dimensional genome.

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Section: Discussionsupporting

confidence: 63%

Section: Methodsmentioning

confidence: 99%

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MCM complexes are barriers that restrict cohesin-mediated loop extrusion

Dequeker

Scherr

Brandão

et al. 2022

Nature

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“…It has been proposed that two separate populations of Rec8 cohesin act on loop formation and cohesion [ 34 ]. In mouse oocyte meiosis, it has been suggested that RAD21/SCC1 and REC8 cohesins have distinct functions in chromatin loop formation and cohesion, respectively [ 36 , 108 ]. Functions of the kleisin subunits in meiotic chromatin structure may differ among species.…”

Section: Roles Of Meiotic Cohesin In Chromosome Architecturementioning

confidence: 99%

“…Even in asynaptic organisms, Rec8 cohesin forms an axial structure resembling the lateral element, which is essential for homologous recombination during meiosis [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. In addition to these canonical roles of Rec8 cohesin in recombination, recent developments in technologies, such as genome-wide chromosome conformation capture, have revealed roles for Rec8 cohesin in meiotic chromosome architecture [ 33 , 34 , 35 , 36 ]. This review highlights the role of Rec8 cohesin in meiosis, which is common in both SC-forming and asynaptic organisms.…”

Section: Introductionmentioning

confidence: 99%

Rec8 Cohesin: A Structural Platform for Shaping the Meiotic Chromosomes

Sakuno

Hiraoka

2022

Genes

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Meiosis is critically different from mitosis in that during meiosis, pairing and segregation of homologous chromosomes occur. During meiosis, the morphology of sister chromatids changes drastically, forming a prominent axial structure in the synaptonemal complex. The meiosis-specific cohesin complex plays a central role in the regulation of the processes required for recombination. In particular, the Rec8 subunit of the meiotic cohesin complex, which is conserved in a wide range of eukaryotes, has been analyzed for its function in modulating chromosomal architecture during the pairing and recombination of homologous chromosomes in meiosis. Here, we review the current understanding of Rec8 cohesin as a structural platform for meiotic chromosomes.

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Macrophage‐derived extracellular vesicles regulate follicular activation and improve ovarian function in old mice by modulating local environment

Xiao

Peng

et al. 2022

Clinical & Translational Med

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In mammals, ovarian function is dependent on the primordial follicle pool and the rate of primordial follicle activation determines a female's reproductive lifespan. Ovarian ageing is characterised by chronic low‐grade inflammation with accelerated depletion of primordial follicles and deterioration of oocyte quality. Macrophages (Mφs) play critical roles in multiple aspects of ovarian functions; however, it remains unclear whether Mφs modulate the primordial follicle pool and what is their role in ovarian ageing. Here, by using super‐ or naturally ovulated mouse models, we demonstrated for the first time that ovulation‐induced local inflammation acted as the driver for selective activation of surrounding primordial follicles in each estrous cycle. This finding was related to infiltrating Mφs in ovulatory follicles and the dynamic changes of the two polarised Mφs, M1 and M2 Mφs, during the process. Further studies on newborn ovaries cocultured with different subtypes of Mφs demonstrated the stimulatory effect of M1 Mφs on primordial follicles, whereas M2 Mφs maintained follicles in a dormant state. The underlying mechanism was associated with the differential regulation of the Phosphatidylinositol 3‐kinase/Mechanistic target of rapamycin (PI3K/mTOR) signaling pathway through secreted extracellular vesicles (EVs) and the containing specific miRNAs miR‐107 (M1 Mφs) and miR‐99a‐5p (M2 Mφs). In aged mice, the intravenous injection of M2‐EVs improved ovarian function and ameliorated the inflammatory microenvironment within the ovary. Thus, based on the anti‐ageing effects of M2 Mφs in old mice, M2‐EVs may represent a new approach to improve inflammation‐related infertility in women.

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Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age

Cited by 35 publications

References 90 publications

MCM complexes are barriers that restrict cohesin-mediated loop extrusion

MCM complexes are barriers that restrict cohesin-mediated loop extrusion

Rec8 Cohesin: A Structural Platform for Shaping the Meiotic Chromosomes

Macrophage‐derived extracellular vesicles regulate follicular activation and improve ovarian function in old mice by modulating local environment

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