.png){kind=icon}
返回
Developmental differences in genome replication program and origin activation
.png){kind=icon}
OA
AI
DOI：10.1093/nar/gkaa1124.png)
.png){kind=icon}
.png){kind=icon}
分享.png){kind=icon}
收藏
摘要
En 中文
To ensure error-free duplication of all (epi)genetic information once per cell cycle, DNA replication follows a cell type and developmental stage specific spatio-temporal program. Here, we analyze the spatio-temporal DNA replication progression in (un)differentiated mouse embryonic stem (mES) cells. Whereas telomeres replicate throughout S-phase, we observe mid S-phase replication of (peri)centromeric heterochromatin in mES cells, which switches to late S-phase replication upon differentiation. This replication timing reversal correlates with and depends on an increase in condensation and a decrease in acetylation of chromatin. We further find synchronous duplication of the Y chromosome, marking the end of S-phase, irrespectively of the pluripotency state. Using a combination of single-molecule and super-resolution microscopy, we measure molecular properties of the mES cell replicon, the number of replication foci active in parallel and their spatial clustering. We conclude that each replication nanofocus in mES cells corresponds to an individual replicon, with up to one quarter representing unidirectional forks. Furthermore, with molecular combing and genome-wide origin mapping analyses, we find that mES cells activate twice as many origins spaced at half the distance than somatic cells. Altogether, our results highlight fundamental developmental differences on progression of genome replication and origin activation in pluripotent cells.
Keyword:
HUMAN Y-CHROMOSOME
EARLY XENOPUS-EMBRYOS
DNA-REPLICATION
S-PHASE
HISTONE ACETYLATION
CELL-CYCLE
CONSTITUTIVE HETEROCHROMATIN
DROSOPHILA-MELANOGASTER
CHROMATIN CONFORMATION
NUCLEAR-ORGANIZATION
AI总结
对已上传原文的论文进行重点信息的提取，主要内容包括：简要概述、研究摘要、背景介绍、关键亮点、图文解析、展望与总结。
期刊
IF:
13.1
论文数:
3.6W
被引数:
29.0W
机构
引用论文
Getting the genome in shape: the formation of loops, domains and compartments.png)
GENOME BIOLOGYOAAI
GENOME BIOLOGYIF9.4
OAAI分享收藏
Preparation of Inactivated Oil-Emulsion Vaccines with Avian Viral or Mycoplasma Antigens禽病毒或支原体抗原灭活油乳剂疫苗的制备
PREAI
分享收藏Targeted manipulation of heterochromatin rescues MeCP2 Rett mutants and re-establishes higher order chromatin organizationNUCLEIC ACIDS RESEARCHOAAI
NUCLEIC ACIDS RESEARCHIF13.1
OAAI分享收藏Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problemBIOESSAYS
BIOESSAYSIF2.7
PREAI
分享收藏
查看更多内容