PMID- 34491983
OWN - NLM
STAT- MEDLINE
DCOM- 20211119
LR  - 20230921
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 19
IP  - 9
DP  - 2021 Sep
TI  - A systemic cell cycle block impacts stage-specific histone modification profiles 
      during Xenopus embryogenesis.
PG  - e3001377
LID - 10.1371/journal.pbio.3001377 [doi]
LID - e3001377
AB  - Forming an embryo from a zygote poses an apparent conflict for epigenetic 
      regulation. On the one hand, the de novo induction of cell fate identities 
      requires the establishment and subsequent maintenance of epigenetic information 
      to harness developmental gene expression. On the other hand, the embryo depends 
      on cell proliferation, and every round of DNA replication dilutes preexisting 
      histone modifications by incorporation of new unmodified histones into chromatin. 
      Here, we investigated the possible relationship between the propagation of 
      epigenetic information and the developmental cell proliferation during Xenopus 
      embryogenesis. We systemically inhibited cell proliferation during the G1/S 
      transition in gastrula embryos and followed their development until the tadpole 
      stage. Comparing wild-type and cell cycle-arrested embryos, we show that the 
      inhibition of cell proliferation is principally compatible with embryo survival 
      and cellular differentiation. In parallel, we quantified by mass spectrometry the 
      abundance of a large set of histone modification states, which reflects the 
      developmental maturation of the embryonic epigenome. The arrested embryos 
      developed abnormal stage-specific histone modification profiles (HMPs), in which 
      transcriptionally repressive histone marks were overrepresented. Embryos released 
      from the cell cycle block during neurulation reverted toward normality on 
      morphological, molecular, and epigenetic levels. These results suggest that the 
      cell cycle block by HUA alters stage-specific HMPs. We propose that this 
      influence is strong enough to control developmental decisions, specifically in 
      cell populations that switch between resting and proliferating states such as 
      stem cells.
FAU - Pokrovsky, Daniil
AU  - Pokrovsky D
AUID- ORCID: 0000-0001-5307-3850
AD  - Ludwig-Maximilians-Universitat Munchen, Planegg-Martinsried, Germany.
FAU - Forne, Ignasi
AU  - Forne I
AUID- ORCID: 0000-0003-0309-907X
AD  - Ludwig-Maximilians-Universitat Munchen, Planegg-Martinsried, Germany.
FAU - Straub, Tobias
AU  - Straub T
AUID- ORCID: 0000-0002-0547-0453
AD  - Ludwig-Maximilians-Universitat Munchen, Planegg-Martinsried, Germany.
FAU - Imhof, Axel
AU  - Imhof A
AUID- ORCID: 0000-0003-2993-8249
AD  - Ludwig-Maximilians-Universitat Munchen, Planegg-Martinsried, Germany.
FAU - Rupp, Ralph A W
AU  - Rupp RAW
AUID- ORCID: 0000-0002-8068-9957
AD  - Ludwig-Maximilians-Universitat Munchen, Planegg-Martinsried, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210907
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (Enzyme Inhibitors)
RN  - 38966-21-1 (Aphidicolin)
RN  - X6Q56QN5QC (Hydroxyurea)
SB  - IM
MH  - Animals
MH  - Aphidicolin/pharmacology
MH  - Cell Cycle
MH  - Cell Proliferation/drug effects
MH  - Embryo, Nonmammalian/embryology
MH  - Enzyme Inhibitors/pharmacology
MH  - *Epigenesis, Genetic
MH  - *Histone Code
MH  - Hydroxyurea/pharmacology
MH  - Xenopus laevis/*embryology
PMC - PMC8535184
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/09/08 06:00
MHDA- 2021/11/20 06:00
PMCR- 2021/09/07
CRDT- 2021/09/07 17:22
PHST- 2020/08/21 00:00 [received]
PHST- 2021/07/30 00:00 [accepted]
PHST- 2021/10/22 00:00 [revised]
PHST- 2021/09/08 06:00 [pubmed]
PHST- 2021/11/20 06:00 [medline]
PHST- 2021/09/07 17:22 [entrez]
PHST- 2021/09/07 00:00 [pmc-release]
AID - PBIOLOGY-D-20-02551 [pii]
AID - 10.1371/journal.pbio.3001377 [doi]
PST - epublish
SO  - PLoS Biol. 2021 Sep 7;19(9):e3001377. doi: 10.1371/journal.pbio.3001377. 
      eCollection 2021 Sep.