Abstract
Song et al. used an allelic reporter approach to show super-enhancers allelic DNA methylation dynamics underlies locus-specific heterogeneity, which functionally impacts transcription and cellular states of mouse embryonic stem cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 905-920.e6 |
| Journal | Molecular Cell |
| Volume | 75 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 5 2019 |
| Externally published | Yes |
Keywords
- dynamic DNA methylation
- embryonic stem cells
- super-enhancers
- transcriptional heterogeneity
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
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In: Molecular Cell, Vol. 75, No. 5, 05.09.2019, p. 905-920.e6.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Dynamic Enhancer DNA Methylation as Basis for Transcriptional and Cellular Heterogeneity of ESCs
AU - Song, Yuelin
AU - van den Berg, Patrick R.
AU - Markoulaki, Styliani
AU - Soldner, Frank
AU - Dall'Agnese, Alessandra
AU - Henninger, Jonathan E.
AU - Drotar, Jesse
AU - Rosenau, Nicholas
AU - Cohen, Malkiel A.
AU - Young, Richard A.
AU - Semrau, Stefan
AU - Stelzer, Yonatan
AU - Jaenisch, Rudolf
N1 - Funding Information: We thank George Bell, Prathapan Thiru, and Bingbing Yuan for their help in ChIP-seq analysis and BS-PCR sequencing analysis; Ruth Flannery and Dina Rooney for their help with animal husbandry, injections of the ESCs, and harvesting pre-implantation embryos; and Dongdong Fu for sectioning and processing of teratoma samples. We would like to thank Tom Volkert, Sumeet Gupta, Kevin Truong, Amanda Chilaka, and Jennifer Love of the Whitehead Genome Technology Core for their help in ChIP-seq; Wendy Salmon of the W.M. Keck Microscopy Facility for help with confocal microscopy; Glenn Paradis, Patti Wisniewski, Patrick Autissier, Michael Jennings, Michele Griffin, Mervelina Saturno-Condon, Hanna Aharonov, and Eleanor Kincaid of the Whitehead Institute and MIT flow cytometry facilities for their help with cell sorting. We thank Dr. Roderick Bronson and Kathleen Cormier at the KI Swanson Biotechnology Center Histology Core for teratoma sample consultation. We thank Raaji Alagappan, Tenzin Lungjangwa, and Carrie Garrett-Engele for their technical support. We thank Alicia V. Zamudio from Young Lab, Jian Shu, Shawn Liu, Haiting Ma, Emile Wogram, and all of the members of the Jaenisch lab for helpful discussions. Y.S. was supported by HFSP long-term fellowship, ISF grant no. 1610/18 and is the incumbent of the Louis and Ida Rich Career Development Chair. R.J. was supported by NIH grants HD 045022, 1U19AI131135, 5R01MH104610, and 1R01GM114864. Y. Song, Y. Stelzer, and R.J. conceived the project. Y. Stelzer and R.J. designed and supervised the experiments, S.S. R.A.Y. and R.J. acquired funding for this study. Y. Song conducted experiments, interpreted results, and wrote the manuscript with input from all authors. S.M. J.D. and N.R. conducted blastocyst injections. S.S. and P.R.v.d.B. performed re-analysis of the published scWGBS data, RNA-seq analysis, and smFISH. A.D. and J.E.H. assisted with DNA FISH, IF, and quantitative image analyses. F.S. assisted with cloning, targeting, and designing of the CRISPR knockout experiments and contributed instrumentally to the writing of the manuscript. M.A.C. assisted with teratoma injection. R.J. is a cofounder of Fate Therapeutics, Fulcrum Therapeutics, and Omega Therapeutics and an advisor to Dewpoint Therapeutics. R.A.Y. is a founder and shareholder of Syros Pharmaceuticals, Camp4 Therapeutics, Omega Therapeutics, and Dewpoint Therapeutics. Funding Information: We thank George Bell, Prathapan Thiru, and Bingbing Yuan for their help in ChIP-seq analysis and BS-PCR sequencing analysis; Ruth Flannery and Dina Rooney for their help with animal husbandry, injections of the ESCs, and harvesting pre-implantation embryos; and Dongdong Fu for sectioning and processing of teratoma samples. We would like to thank Tom Volkert, Sumeet Gupta, Kevin Truong, Amanda Chilaka, and Jennifer Love of the Whitehead Genome Technology Core for their help in ChIP-seq; Wendy Salmon of the W.M. Keck Microscopy Facility for help with confocal microscopy; Glenn Paradis, Patti Wisniewski, Patrick Autissier, Michael Jennings, Michele Griffin, Mervelina Saturno-Condon, Hanna Aharonov, and Eleanor Kincaid of the Whitehead Institute and MIT flow cytometry facilities for their help with cell sorting. We thank Dr. Roderick Bronson and Kathleen Cormier at the KI Swanson Biotechnology Center Histology Core for teratoma sample consultation. We thank Raaji Alagappan, Tenzin Lungjangwa, and Carrie Garrett-Engele for their technical support. We thank Alicia V. Zamudio from Young Lab, Jian Shu, Shawn Liu, Haiting Ma, Emile Wogram, and all of the members of the Jaenisch lab for helpful discussions. Y.S. was supported by HFSP long-term fellowship , ISF grant no. 1610/18 and is the incumbent of the Louis and Ida Rich Career Development Chair . R.J. was supported by NIH grants HD 045022 , 1U19AI131135 , 5R01MH104610 , and 1R01GM114864 . Publisher Copyright: © 2019 Elsevier Inc.
PY - 2019/9/5
Y1 - 2019/9/5
N2 - Song et al. used an allelic reporter approach to show super-enhancers allelic DNA methylation dynamics underlies locus-specific heterogeneity, which functionally impacts transcription and cellular states of mouse embryonic stem cells.
AB - Song et al. used an allelic reporter approach to show super-enhancers allelic DNA methylation dynamics underlies locus-specific heterogeneity, which functionally impacts transcription and cellular states of mouse embryonic stem cells.
KW - dynamic DNA methylation
KW - embryonic stem cells
KW - super-enhancers
KW - transcriptional heterogeneity
UR - http://www.scopus.com/inward/record.url?scp=85071542699&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071542699&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2019.06.045
DO - 10.1016/j.molcel.2019.06.045
M3 - Article
C2 - 31422875
AN - SCOPUS:85071542699
SN - 1097-2765
VL - 75
SP - 905-920.e6
JO - Molecular Cell
JF - Molecular Cell
IS - 5
ER -