Advances in epigenetics link genetics to the environment and disease

Nature, Год журнала: 2019, Номер 571(7766), С. 489 - 499

Опубликована: Июль 1, 2019

Язык: Английский

---

Chromatin replication and epigenetic cell memory

Nature Cell Biology, Год журнала: 2020, Номер 22(4), С. 361 - 371

Опубликована: Март 30, 2020

Язык: Английский

---

The Mcm2-Ctf4-Polα Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands

Molecular Cell, Год журнала: 2018, Номер 72(1), С. 140 - 151.e3

Опубликована: Сен. 20, 2018

Язык: Английский

---

Active and Repressed Chromatin Domains Exhibit Distinct Nucleosome Segregation during DNA Replication

Cell, Год журнала: 2019, Номер 179(4), С. 953 - 963.e11

Опубликована: Окт. 1, 2019

Язык: Английский

---

Recycling of modified H2A-H2B provides short-term memory of chromatin states

Cell, Год журнала: 2023, Номер 186(5), С. 1050 - 1065.e19

Опубликована: Фев. 6, 2023

Chromatin landscapes are disrupted during DNA replication and must be restored faithfully to maintain genome regulation cell identity. The histone H3-H4 modification landscape is by parental recycling of new histones. How impacts on H2A-H2B currently unknown. Here, we measure modifications H2A.Z across the cycle using quantitative genomics. We show that H2AK119ub1, H2BK120ub1, recycled accurately replication. Modified segregated symmetrically daughter strands via POLA1 lagging strand, but independent recycling. Post-replication, variant quickly restored, H2AK119ub1 guides accurate restoration H3K27me3. This work reveals epigenetic transmission identifies cross talk between in epigenome propagation. propose rapid short-term memory facilitates stable chromatin states.

Язык: Английский

---

Symmetric inheritance of parental histones governs epigenome maintenance and embryonic stem cell identity

Nature Genetics, Год журнала: 2023, Номер 55(9), С. 1567 - 1578

Опубликована: Сен. 1, 2023

Modified parental histones are segregated symmetrically to daughter DNA strands during replication and can be inherited through mitosis. How this may sustain the epigenome cell identity remains unknown. Here we show that transmission of histone-based information maintains fidelity embryonic stem plasticity. Asymmetric segregation H3-H4 in MCM2-2A mutants compromised mitotic inheritance histone modifications globally altered epigenome. This included widespread spurious deposition repressive modifications, suggesting elevated epigenetic noise. Moreover, H3K9me3 loss at repeats caused derepression H3K27me3 redistribution across bivalent promoters correlated with misexpression developmental genes. mutation challenged dynamic transitions cellular states cycle, enhancing naïve pluripotency reducing lineage priming G1. Furthermore, competence was diminished, correlating impaired exit from pluripotency. Collectively, argues a correctly balanced chromatin landscape able support mammalian differentiation.

Язык: Английский

---

Parental histone transfer caught at the replication fork

Nature, Год журнала: 2024, Номер 627(8005), С. 890 - 897

Опубликована: Март 6, 2024

Язык: Английский

---

The fork protection complex promotes parental histone recycling and epigenetic memory

Cell, Год журнала: 2024, Номер 187(18), С. 5029 - 5047.e21

Опубликована: Авг. 1, 2024

The inheritance of parental histones across the replication fork is thought to mediate epigenetic memory. Here, we reveal that fission yeast Mrc1 (CLASPIN in humans) binds H3-H4 tetramers and operates as a central coordinator symmetric histone inheritance. mutants key connector domain disrupted segregation lagging strand comparable Mcm2 histone-binding mutants. Both showed clonal asymmetric loss H3K9me-mediated gene silencing. AlphaFold predicted co-chaperoning by Mcm2, with bridging binding. Biochemical functional analysis validated this model revealed duality function: disabling binding lagging-strand recycling while another mutation impaired leading recycling. We propose toggles between pathways, part intra-replisome co-chaperoning, ensure transmission both daughter cells.

Язык: Английский

---

POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication

Molecular Cell, Год журнала: 2018, Номер 72(1), С. 112 - 126.e5

Опубликована: Сен. 11, 2018

Maintenance of epigenetic integrity relies on coordinated recycling and partitioning parental histones deposition newly synthesized during DNA replication. This process depends upon a poorly characterized network histone chaperones, remodelers, binding proteins. Here we implicate the POLE3-POLE4 subcomplex leading-strand polymerase, Polε, in replication-coupled nucleosome assembly through its ability to selectively bind H3-H4. Using hydrogen/deuterium exchange mass spectrometry physical mapping, define minimal domains necessary for interaction between Biochemical analyses establish that is chaperone promotes tetrasome formation supercoiling vitro. In cells, binds both histones, depletion hinders helicase unwinding chromatin PCNA unloading compromises retention new deposition. Collectively, our study reveals possesses intrinsic H3-H4 activity, which facilitates faithful dynamics at replication fork.

Язык: Английский

---

Kinetics and mechanisms of mitotic inheritance of DNA methylation and their roles in aging-associated methylome deterioration

Cell Research, Год журнала: 2020, Номер 30(11), С. 980 - 996

Опубликована: Июнь 24, 2020

Язык: Английский

---