Polycomb Regulates Mesoderm Cell Fate-Specification in Embryonic Stem Cells through Activation and Repression Mechanisms

Cell Stem Cell
Lluis MoreyLuciano Di Croce

Abstract

Polycomb complexes (PRC1 and PRC2) are essential regulators of epigenetic gene silencing in embryonic and adult stem cells. Emerging evidence suggests that the core subunit composition regulates distinct biological processes, yet little is known about the mechanistic underpinnings of how differently composed Polycomb complexes instruct and maintain cell fate. Here we find that Mel18, also known as Pcgf2 and one of six Pcgf paralogs, uniquely regulates PRC1 to specify mesoderm cell fate in embryonic stem cells. Mechanistically, Mel18 functions as a classical Polycomb protein during early cardiac mesoderm differentiation by repressing pluripotency, lineage specification, late cardiac differentiation, and negative regulators of the BMP pathway. However, Mel18 also positively regulates expression of key mesoderm transcription factors, revealing an unexpected function of Mel18 in gene activation during cardiac differentiation. Taken together, our findings reveal that Mel18 is required to specify PRC1 function in both a context- and stage-specific manner.

References

Sep 24, 2004·Nature·Hengbin WangYi Zhang
Jun 17, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dusan ZencakYvan Arsenijevic
Jun 21, 2005·Genes & Development·Sophia W M BruggemanMaarten van Lohuizen
May 23, 2006·The Journal of Biological Chemistry·Zhizhong LiRui-Ming Xu
Mar 30, 2010·Trends in Biochemical Sciences·Lluís Morey, Kristian Helin
Jun 3, 2011·Cardiovascular Research·Robert DavidWolfgang-Michael Franz
Jun 20, 2012·FEBS Letters·Marie-Christine Ramel, Caroline S Hill
Jul 10, 2012·Cell Stem Cell·Nuno Miguel LuisSalvador Aznar Benitah
Mar 5, 2013·Cold Spring Harbor Perspectives in Biology·Benoit G Bruneau
May 30, 2013·Development·April M CraftGordon M Keller
Oct 8, 2013·Nature Structural & Molecular Biology·Luciano Di Croce, Kristian Helin
Jan 23, 2014·Genes & Development·Luigi AloiaLuciano Di Croce
Jun 7, 2014·Cell Stem Cell·Anne Laugesen, Kristian Helin
Aug 2, 2014·Cell·Bérénice A BenayounAnne Brunet
Dec 19, 2014·Nature·Zhonghua GaoDanny Reinberg

❮ Previous
Next ❯

Citations

Dec 30, 2015·The Journal of Cell Biology·Idan Cohen, Elena Ezhkova
Mar 5, 2016·Cell Stem Cell·Yang ZhouLi Qian
May 7, 2016·Current Opinion in Genetics & Development·Diego Pasini, Luciano Di Croce
May 21, 2016·Trends in Cell Biology·Marianne EntrevanGiacomo Cavalli
Jun 14, 2016·Nature Structural & Molecular Biology·Susan L KloetMichiel Vermeulen
Aug 9, 2016·Molecular Cell·Zoltan SimandiLaszlo Nagy
Oct 26, 2016·Journal of Molecular Biology·M Wassef, R Margueron
Oct 19, 2016·Cell Cycle·Aysegül Kaymak, Holger Richly
Jan 15, 2017·Experimental Hematology·Miguel Vidal, Katarzina Starowicz
Jan 26, 2017·Epigenetics : Official Journal of the DNA Methylation Society·Gabrijela DumbovicSonia-V Forcales
Apr 21, 2017·Nucleic Acids Research·Andrew P HutchinsDuanqing Pei
May 26, 2017·Statistics in Medicine·Jing QianAndrea S Foulkes
Nov 2, 2017·Nature Communications·Alexandra SantanachLuciano Di Croce
Aug 30, 2018·Physiological Reviews·Thomas Moore-MorrisMichel Puceat
Jul 13, 2016·Molecular and Cellular Biology·Sergi ArandaLuciano Di Croce
Feb 13, 2018·Journal of Molecular Cell Biology·Xiangdong LvYun Zhao
Feb 23, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Vincent LoubiereGiacomo Cavalli
Apr 17, 2019·Genetic Testing and Molecular Biomarkers·Xiaonian ZhuShengkui Tan
Oct 21, 2018·The Journal of Cell Biology·Valerio Di CarloLuciano Di Croce
Jun 11, 2019·Expert Opinion on Therapeutic Targets·Maïka JangalMichael Witcher
Mar 21, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Idan CohenElena Ezhkova
May 23, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Judit SymmankGeraldine Zimmer-Bensch
May 23, 2020·Genes & Development·Shelagh BoyleRobert S Illingworth
Jul 17, 2020·PloS One·Surya HenryMelinda Katalin Pirity
Aug 4, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Claudia Gentile, Marie Kmita
Sep 18, 2020·Nucleic Acids Research·Yuliang Feng, Siim Pauklin
Sep 19, 2018·Nature Genetics·Glòria MasLuciano Di Croce
Sep 29, 2018·Journal of the National Cancer Institute·Jeong-Yeon LeeGu Kong
Jun 27, 2019·Nature Cell Biology·Tian V TianThomas Graf
Nov 5, 2019·Frontiers in Cell and Developmental Biology·Valentina GambacortaRaffaella Di Micco
Jan 30, 2018·Journal of the American Statistical Association·Sihai Dave ZhaoHongzhe Li
Nov 14, 2018·Cellular and Molecular Life Sciences : CMLS·Seyedeh-Nafiseh HassaniHossein Baharvand
Sep 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·James M GahanChristine E Schnitzler
May 17, 2018·Nature Communications·Mingze YaoHongjie Yao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiac Regeneration

Cardiac regeneration enables the repair of irreversibly damaged heart tissue using cutting-edge science, including stem cell and cell-free therapy. Discover the latest research on cardiac regeneration here.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Cardiovascular Homeostasis

Cardiovascular regulation and homeostasis is important in maintaining health and dysfunction may lead to cardiovascular diseases. Nitric oxide and vascular endothelium are one of many molecules involved in the homeostatic mechanism. Here is the latest research on cardiovascular homeostasis.