TY - JOUR
T1 - Asf1a resolves bivalent chromatin domains for the induction of lineage-specific genes during mouse embryonic stem cell differentiation
AU - Gao, Yuan
AU - Gan, Haiyun
AU - Lou, Zhenkun
AU - Zhang, Zhiguo
N1 - Funding Information:
We thank Dr. Tom Fazzio for E14 stem cell lines, LIF-expression plasmids, and protocols and Drs. Dong Fang, Xiangdong Lv, and Minjie Zhang for reading this manuscript. This work was supported by National Institute of Health Grant GM119015 (to Z.Z.).
Funding Information:
ACKNOWLEDGMENTS. We thank Dr. Tom Fazzio for E14 stem cell lines, LIF-expression plasmids, and protocols and Drs. Dong Fang, Xiangdong Lv, and Minjie Zhang for reading this manuscript. This work was supported by National Institute of Health Grant GM119015 (to Z.Z.).
Publisher Copyright:
© 2018 National Academy of Sciences. All Rights Reserved.
PY - 2018/7/3
Y1 - 2018/7/3
N2 - Bivalent chromatin domains containing repressive H3K27me3 and active H3K4me3 modifications are barriers for the expression of lineage-specific genes in ES cells and must be resolved for the transcription induction of these genes during differentiation, a process that remains largely unknown. Here, we show that Asf1a, a histone chaperone involved in nucleosome assembly and disassembly, regulates the resolution of bivalent domains and activation of lineage-specific genes during mouse ES cell differentiation. Deletion of Asf1a does not affect the silencing of pluripotent genes, but compromises the expression of lineage-specific genes during ES cell differentiation. Mechanistically, the Asf1a–histone interaction, but not the role of Asf1a in nucleosome assembly, is required for gene transcription. Asf1a is recruited to several bivalent promoters, partially through association with transcription factors, and mediates nucleosome disassembly during differentiation. We suggest that Asf1a-mediated nucleosome disassembly provides a means for resolution of bivalent domain barriers for induction of lineage-specific genes during differentiation.
AB - Bivalent chromatin domains containing repressive H3K27me3 and active H3K4me3 modifications are barriers for the expression of lineage-specific genes in ES cells and must be resolved for the transcription induction of these genes during differentiation, a process that remains largely unknown. Here, we show that Asf1a, a histone chaperone involved in nucleosome assembly and disassembly, regulates the resolution of bivalent domains and activation of lineage-specific genes during mouse ES cell differentiation. Deletion of Asf1a does not affect the silencing of pluripotent genes, but compromises the expression of lineage-specific genes during ES cell differentiation. Mechanistically, the Asf1a–histone interaction, but not the role of Asf1a in nucleosome assembly, is required for gene transcription. Asf1a is recruited to several bivalent promoters, partially through association with transcription factors, and mediates nucleosome disassembly during differentiation. We suggest that Asf1a-mediated nucleosome disassembly provides a means for resolution of bivalent domain barriers for induction of lineage-specific genes during differentiation.
KW - Bivalent chromatin domain
KW - Embryonic stem cell differentiation
KW - Histone chaperone
KW - Nucleosome disassembly
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U2 - 10.1073/pnas.1801909115
DO - 10.1073/pnas.1801909115
M3 - Article
C2 - 29915027
AN - SCOPUS:85049358707
SN - 0027-8424
VL - 115
SP - E6162-E6171
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 27
ER -