TY - JOUR
T1 - Quantitative dynamics of chromatin remodeling during germ cell specification from mouse embryonic stem cells
AU - Kurimoto, Kazuki
AU - Yabuta, Yukihiro
AU - Hayashi, Katsuhiko
AU - Ohta, Hiroshi
AU - Kiyonari, Hiroshi
AU - Mitani, Tadahiro
AU - Moritoki, Yoshinobu
AU - Kohri, Kenjiro
AU - Kimura, Hiroshi
AU - Yamamoto, Takuya
AU - Katou, Yuki
AU - Shirahige, Katsuhiko
AU - Saitou, Mitinori
N1 - Funding Information:
We thank H. Sasaki, K. Shirane, T. Abe, and M. Yamaji for discussion and R. Kabata, S. Ohsako, N. Konishi, S. Watanabe, M. Kabata, and T. Satoh for their assistance. We used the supercomputer of ACCMS, Kyoto University. The authors were supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan , by JST-CREST/ERATO , by the Takeda Science Foundation , and by the Tanabe Medical Frontier Conference .
PY - 2015/5/7
Y1 - 2015/5/7
N2 - Germ cell specification is accompanied by epigenetic remodeling, the scale and specificity of which are unclear. Here, we quantitatively delineate chromatin dynamics during induction of mouse embryonic stem cells (ESCs) to epiblast-like cells (EpiLCs) and from there into primordial germ cell-like cells (PGCLCs), revealing large-scale reorganization of chromatin signatures including H3K27me3 and H3K9me2 patterns. EpiLCs contain abundant bivalent gene promoters characterized by low H3K27me3, indicating a state primed for differentiation. PGCLCs initially lose H3K4me3 from many bivalent genes but subsequently regain this mark with concomitant upregulation of H3K27me3, particularly at developmental regulatory genes. PGCLCs progressively lose H3K9me2, including at lamina-associated perinuclear heterochromatin, resulting in changes in nuclear architecture. T recruits H3K27ac to activate BLIMP1 and early mesodermal programs during PGCLC specification, which is followed by BLIMP1-mediated repression of a broad range of targets, possibly through recruitment and spreading of H3K27me3. These findings provide a foundation for reconstructing regulatory networks of the germline epigenome.
AB - Germ cell specification is accompanied by epigenetic remodeling, the scale and specificity of which are unclear. Here, we quantitatively delineate chromatin dynamics during induction of mouse embryonic stem cells (ESCs) to epiblast-like cells (EpiLCs) and from there into primordial germ cell-like cells (PGCLCs), revealing large-scale reorganization of chromatin signatures including H3K27me3 and H3K9me2 patterns. EpiLCs contain abundant bivalent gene promoters characterized by low H3K27me3, indicating a state primed for differentiation. PGCLCs initially lose H3K4me3 from many bivalent genes but subsequently regain this mark with concomitant upregulation of H3K27me3, particularly at developmental regulatory genes. PGCLCs progressively lose H3K9me2, including at lamina-associated perinuclear heterochromatin, resulting in changes in nuclear architecture. T recruits H3K27ac to activate BLIMP1 and early mesodermal programs during PGCLC specification, which is followed by BLIMP1-mediated repression of a broad range of targets, possibly through recruitment and spreading of H3K27me3. These findings provide a foundation for reconstructing regulatory networks of the germline epigenome.
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U2 - 10.1016/j.stem.2015.03.002
DO - 10.1016/j.stem.2015.03.002
M3 - Article
C2 - 25800778
AN - SCOPUS:84929281565
VL - 16
SP - 517
EP - 532
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 5
ER -