Article
Genetics & Heredity
Zhiyuan Chen, Mohamed Nadhir Djekidel, Yi Zhang
Summary: In mouse preimplantation embryos, H2AK119ub1 and H3K27me3 have distinct genome-wide dynamics. Loss of H2AK119ub1 results in premature activation of developmental genes, while loss of H3K27me3 does not.
Review
Biochemistry & Molecular Biology
Michelle M. Mitchener, Tom W. Muir
Summary: Research over the past decade has revealed a new layer of epigenetic dysregulation, uncovering the association between somatic missense mutations in histones and human pathologies, especially cancer. While some of these mutations are believed to be key drivers of cancer, the effects of the majority of them on disease onset and progression are still unclear. Studies have shown that even at low dosage, histone mutants can corrupt chromatin states, providing insights into the intricate mechanisms of epigenetic control.
Article
Biochemistry & Molecular Biology
Junjie Li, Qi Li, Wentao Wang, Xinran Zhang, Chen Chu, Xintian Tang, Bo Zhu, Lizhong Xiong, Yu Zhao, Dao-Xiu Zhou
Summary: DELLA proteins are important regulators of gibberellic acid signaling and have contributed to grain yield increases in rice and wheat varieties during the green revolution. This study identifies a complex involving the rice DELLA protein SLENDER RICE1 (SLR1), Polycomb-repressive complex 2 (PRC2), and histone deacetylase HDA702, which represses downstream genes through silent chromatin state formation. Disruption of this complex impairs SLR1-dependent histone modification and gene repression, highlighting the importance of chromatin regulators in DELLA-mediated gene regulation.
Review
Oncology
Xiuli Liu, Xin Liu
Summary: Polycomb repressive complex 2 (PRC2) is a histone-modifying enzyme complex involved in gene silencing and development, and its dysregulation is associated with cancer and developmental disorders. This article reviews the current understanding of the cellular regulation of PRC2 function, particularly focusing on H3K27 methylation and chromatin targeting, and discusses PRC2-related disease mechanisms. The mode of action of PRC2 in gene regulation, including competition with acetylation, crosstalk with transcription machinery, and chromatin structure formation, is summarized. Recent progress in the structural biology of PRC2, such as complex assembly, enzyme catalysis, and chromatin recruitment, is highlighted, providing valuable insights into the stability and plasticity of developmental transcriptional programs impacted by PRC2.
FRONTIERS IN ONCOLOGY
(2022)
Article
Plant Sciences
Linhao Xu, Jinping Cheng, Hua Jiang
Summary: This study demonstrates that H3S28 is crucial for PRC2-dependent H3K27me3-mediated gene silencing in Arabidopsis. Mutating H3S28A leads to an early-flowering phenotype and increased expression of flowering-promoting genes. Contrary to expectations, the H3S28A mutation decreases H3K27me3 levels.
Article
Multidisciplinary Sciences
Jia-Ray Yu, Gary LeRoy, Devin Bready, Joshua D. Frenster, Ricardo Saldana-Meyer, Ying Jin, Nicolas Descostes, James M. Stafford, Dimitris G. Placantonakis, Danny Reinberg
Summary: The study identified that H3K36me2 promotes tumorigenesis in H3K27M-DIPG by affecting the writing activity of NSD1 and NSD2, as well as the reading factors LEDGF and HDGF2. Loss of NSD1/2 impedes cellular proliferation and tumorigenesis.
Article
Biochemistry & Molecular Biology
Huitao Fan, Yiran Guo, Yi-Hsuan Tsai, Aaron J. Storey, Arum Kim, Weida Gong, Ricky D. Edmondson, Samuel G. Mackintosh, Haitao Li, Stephanie D. Byrum, Alan J. Tackett, Ling Cai, Gang Greg Wang
Summary: Trimethylation of histone H3 lysine 27 (H3K27me3) plays a crucial role in gene silencing and imprinting, (epi)genome organization, and organismal development. This study reveals that the Bromo Adjacent Homology (BAH) domain within BAH domain-containing protein 1 (BAHD1) is essential for the targeting of BAHD1 to chromatin and optimal repression of H3K27me3-demarcated genes in mammalian cells. Disruption of the direct interaction between BAHD1(BAH) and H3K27me3 leads to chromatin remodeling and increased histone acetylation at Polycomb gene targets, affecting embryonic development.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Plant Sciences
Justin Su, Zhujun Yao, Yixuan Wu, Joohyun Lee, Jeeyon Jeong
Summary: This article mainly introduces the latest understanding of chromatin-based regulation of iron homeostasis in plants, highlighting recent studies in Arabidopsis and rice. Understanding iron homeostasis in plants is crucial as it is relevant to fundamental biological questions, agriculture, biofortification, and human health.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Melanie Pailles, Melanie Hirlemann, Vincent Brochard, Martine Chebrout, Jean-Francois Oudin, Hendrik Marks, Alice Jouneau, Amelie Bonnet-Garnier
Summary: Early mouse development involves structural and epigenetic changes, including DNA methylation and histone modifications such as H3K27me3. This study investigated the dynamics of H3K27me3 at pericentromeric heterochromatin (PCH) during early development and its role in defining embryonic cells. The results suggest that H3K27me3, along with H3K9me3, is a defining feature of embryonic cells in vivo and may play a role in preserving genomic integrity during relaxed chromatin state. The study also found differences in epigenetic regulation of constitutive heterochromatin between in vitro and in embryo conditions.
SCIENTIFIC REPORTS
(2022)
Review
Cell Biology
Shihang Zhou, Hongliang Zeng, Jinhua Huang, Li Lei, Xiaoliang Tong, Si Li, Ying Zhou, Haoran Guo, Manal Khan, Liping Luo, Rong Xiao, Jing Chen, Qinghai Zeng
Summary: Melanogenesis is a complex process involving multiple genes and signaling pathways, with epigenetics playing a key role in regulating the expression of key genes. Epigenetic-based therapy provides novel opportunities for treating dermatoses caused by pigmentation disturbances.
AGEING RESEARCH REVIEWS
(2021)
Article
Multidisciplinary Sciences
Haining Zhou, Chad B. Stein, Tiasha A. Shafiq, Gergana Shipkovenska, Marian Kalocsay, Joao A. Paulo, Jiuchun Zhang, Zhenhua Luo, Steven P. Gygi, Karen Adelman, Danesh Moazed
Summary: Polycomb repressive complexes (PRCs) and the RIX1 complex work together to silence Polycomb target genes in human cells, with the recruitment of the RIX1 complex to chromatin being essential for silencing.
Article
Cell Biology
Nadezda A. Fursova, Anne H. Turberfield, Neil P. Blackledge, Emma L. Findlater, Anna Lastuvkova, Miles K. Huseyin, Paula Dobrinic, Robert J. Klose
Summary: Histone modifications play crucial roles in gene regulation and development, with little known about modifications found broadly throughout the genome. BAP1 deubiquitylase constrains H2AK119ub1 accumulation throughout the genome, impacting gene expression and transcription. Failure to constrain H2AK119ub1 compromises Polycomb complex occupancy at certain target genes, resulting in their derepression.
GENES & DEVELOPMENT
(2021)
Article
Cell Biology
Yamato Fukui, Yasushi Hirota, Shizu Aikawa, Akihiko Sakashita, Ryoko Shimizu-Hirota, Norihiko Takeda, Chihiro Ishizawa, Rei Iida, Tetsuaki Kaku, Tomoyuki Hirata, Takehiro Hiraoka, Shun Akaeda, Mitsunori Matsuo, Yutaka Osuga
Summary: Infertility affects 15% of couples worldwide, with recurrent implantation failure (RIF) being a major issue in IVF-ET programs. This study revealed that a uterine gene network regulated by the polycomb repressive complex 2 (PRC2) controls embryo implantation. Dysregulation of PRC2 components and target genes was observed in patients with RIF. Knockout mice studies showed that stromal Ezh2 plays a crucial role in female fertility. This research highlighted the importance of the EZH2-PRC2-H3K27me3 axis in preparing the endometrium for successful embryo invasion.
CELL DEATH & DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Amira Fitieh, Andrew J. Locke, Mobina Motamedi, Ismail Hassan Ismail
Summary: Polycomb group proteins play roles in stem cell maintenance, gene silencing, and DNA damage repair. BMI1, a member of PRC1, is involved in DNA repair and genome integrity, making it a potential pharmacological target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Daniel N. Weinberg, Phillip Rosenbaum, Xiao Chen, Douglas Barrows, Cynthia Horth, Matthew R. Marunde, Irina K. Popova, Zachary B. Gillespie, Michael-Christopher Keogh, Chao Lu, Jacek Majewski, C. David Allis
Summary: The study found that mutations in the DNMT3A PWWP domain identified in paragangliomas and microcephalic dwarfism promote aberrant localization of DNMT3A to CGIs in a PRC1-dependent manner. DNMT3A PWWP mutants accumulate at regions containing PRC1-mediated formation of monoubiquitylated histone H2A lysine 119 (H2AK119ub), irrespective of the amounts of PRC2-catalyzed formation of trimethylated histone H3 lysine 27 (H3K27me3). DNMT3A interacts with H2AK119ub-modified nucleosomes through a putative amino-terminal ubiquitin-dependent recruitment region, providing an alternative form of DNMT3A genomic targeting that is augmented by the loss of PWWP reader function.
Article
Biochemistry & Molecular Biology
Huan Meng, David J. Harrison, Richard R. Meehan
JOURNAL OF CELLULAR BIOCHEMISTRY
(2015)
Review
Pharmacology & Pharmacy
Isabelle R. Miousse, Richard Currie, Kaushik Datta, Heidrun Ellinger-Ziegelbauer, John E. French, Alison H. Harrill, Igor Koturbash, Michael Lawton, Derek Mann, Richard R. Meehan, Jonathan G. Moggs, Raegan O'Lone, Reza J. Rasoulpour, Renee A. Reijo Pera, Karol Thompson
Article
Oncology
John P. Thomson, Raffaele Ottaviano, Elif B. Unterberger, Harri Lempiainen, Arne Muller, Remi Terranova, Robert S. Illingworth, Shaun Webb, Alastair R. W. Kerr, Marcus J. Lyall, Amanda J. Drake, C. Roland Wolf, Jonathan G. Moggs, Michael Schwarz, Richard R. Meehan
Article
Cell Biology
Colm E. Nestor, Antonio Lentini, Cathrine Hagg Nilsson, Danuta R. Gawel, Mika Gustafsson, Lina Mattson, Hui Wang, Olof Rundquist, Richard R. Meehan, Bernward Klocke, Martin Seifert, Stefanie M. Hauck, Helmut Laumen, Huan Zhang, Mikael Benson
Article
Biochemistry & Molecular Biology
Natasha Vafadar-Isfahani, Christina Parr, Lara E. McMillan, Juliane Sanner, Zhao Yeo, Stephen Saddington, Oliver Peacock, Hazel A. Cruickshanks, Richard R. Meehan, Jonathan N. Lund, Cristina Tufarelli
Article
Multidisciplinary Sciences
Alexander Raven, Wei-Yu Lu, Tak Yung Man, Sofia Ferreira-Gonzalez, Eoghan O'Duibhir, Benjamin J. Dwyer, John P. Thomson, Richard R. Meehan, Roman Bogorad, Victor Koteliansky, Yuri Kotelevtsev, Charles Ffrench-Constant, Luke Boulter, Stuart J. Forbes
Correction
Genetics & Heredity
Natalie D. Shaw, Harrison Brand, Zachary A. Kupchinsky, Hemant Bengani, Lacey Plummer, Takako I. Jones, Serkan Erdin, Kathleen A. Williamson, Joe Rainger, Alexei Stortchevoi, Kaitlin Samocha, Benjamin B. Currall, Donncha S. Dunican, Ryan L. Collins, Jason R. Willer, Angela Lek, Monkol Lek, Malik Nassan, Shahrin Pereira, Tammy Kammin, Diane Lucente, Alexandra Silva, Catarina M. Seabra, Colby Chiang, Yu An, Morad Ansari, Jacqueline K. Rainger, Shelagh Joss, Jill Clayton Smith, Margaret F. Lippincott, Sylvia S. Singh, Nirav Patel, Jenny W. Jing, Jennifer R. Law, Nalton Ferraro, Alain Verloes, Anita Rauch, Katharina Steindl, Markus Zweier, Ianina Scheer, Daisuke Sato, Nobuhiko Okamoto, Christina Jacobsen, Jeanie Tryggestad, Steven Chernausek, Lisa A. Schimmenti, Benjamin Brasseur, Claudia Cesaretti, Jose E. Garcia-Ortiz, Tatiana Pineda Buitrago, Orlando Perez Silva, Jodi D. Hoffman, Wolfgang Muhlbauer, Klaus W. Ruprecht, Bart L. Loeys, Masato Shino, Angela M. Kaindl, Chie-Hee Cho, Cynthia C. Morton, Richard R. Meehan, Veronica Van Heyningen, Eric C. Liao, Ravikumar Balasubramanian, Janet E. Hall, Stephanie B. Seminara, Daniel Macarthur, Steven A. Moore, Koh-ichiro Yoshiura, James F. Gusella, Joseph A. Marsh, John M. Graham, Angela E. Lin, Nicholas Katsanis, Peter L. Jones, William F. Crowley, Erica E. Davis, David R. FitzPatrick, Michael E. Talkowski
Article
Genetics & Heredity
Natalie D. Shaw, Harrison Brand, Zachary A. Kupchinsky, Hemant Bengani, Lacey Plummer, Takako I. Jones, Serkan Erdin, Kathleen A. Williamson, Joe Rainger, Alexei Stortchevoi, Kaitlin Samocha, Benjamin B. Curra, Donncha S. Dunican, Ryan L. Collins, Jason R. Willer, Angela Lek, Monkol Lek, Malik Nassan, Shahrin Pereira, Tammy Kammin, Diane Lucente, Alexandra Silva, Catarina M. Seabra, Colby Chiang, Yu Ana, Morad Ansari, Jacqueline K. Rainger, Shelagh Joss, Jill Clayton Smith, Margaret F. Lippincott, Sylvia S. Singh, Nirav Patel, Jenny W. Jing, Jennifer R. Law, Nalton Ferraro, Main Verloes, Anita Rauch, Katharina Steindl, Markus Zweier, Ianina Scheer, Daisuke Sato, Nobuhiko Okamoto, Christina Jacobsen, Jeanie Tryggestad, Steven Chernausek, Lisa A. Schimmenti, Benjamin Brasseur, Claudia Cesaretti, Jose E. Garcia-Ortiz, Tatiana Pineda Buitrago, Orlando Perez Silva, Jodi D. Hoffman, Wolfgang Muehlbauer, Klaus W. Ruprecht, Bart L. Loeys, Masato Shino, Angela M. Kaind, Chie-Hee Cho, Cynthia C. Morton, Richard R. Meehan, Veronica van Heyningen, Eric C. Liao, Ravikumar Balasubramanian, Janet E. Hall, Stephanie B. Seminara, Daniel Macarthur, Steven A. Moore, Koh-ichiro Yoshiura, James F. Gusella, Joseph A. Marsh, John M. Graham, Angela E. Lin, Nicholas Katsanis, Peter L. Jones, William F. Crowley, Erica E. Davis, David R. FitzPatrick, Michael E. Talkowski
Article
Biology
Marie MacLennan, Marta Garcia-Canadas, Judith Reichmann, Elena Khazina, Gabriele Wagner, Christopher J. Playfoot, Carmen Salvador-Palomeque, Abigail R. Mann, Paula Peressini, Laura Sanchez, Karen Dobie, David Read, Chao-Chun Hung, Ragnhild Eskeland, Richard R. Meehan, Oliver Weichenrieder, Jose Luis Garcia-Perez, Ian R. Adams
Article
Biochemical Research Methods
Antonio Lentini, Cathrine Lagerwall, Svante Vikingsson, Heidi K. Mjoseng, Karolos Douvlataniotis, Hartmut Vogt, Henrik Green, Richard R. Meehan, Mikael Benson, Colm E. Nestor
Article
Multidisciplinary Sciences
Darren A. Cusanovich, James P. Reddington, David A. Garfield, Riza M. Daza, Delasa Aghamirzaie, Raquel Marco-Ferreres, Hannah A. Pliner, Lena Christiansen, Xiaojie Qiu, Frank J. Steemers, Cole Trapnell, Jay Shendure, Eileen E. M. Furlong
Article
Multidisciplinary Sciences
Matthew C. Sinton, Jose Meseguer-Ripolles, Baltasar Lucendo-Villarin, Sara Wernig-Zorc, John P. Thomson, Roderick N. Carter, Marcus J. Lyall, Paul D. Walker, Alpesh Thakker, Richard R. Meehan, Gareth G. Lavery, Nicholas M. Morton, Christian Ludwig, Daniel A. Tennant, David C. Hay, Amanda J. Drake
Summary: This study introduces a human pluripotent stem cell-derived model of hepatic steatosis that overcomes challenges and provides new insights. Respirometry and transcriptomic analyses revealed compromised electron transport chain activity, while C-13 isotopic tracing studies showed enhanced TCA cycle anaplerosis and development of a compensatory purine nucleotide cycle shunt. This reproducible and scalable model overcomes challenges in studying mitochondrial metabolism in current models.
Article
Biotechnology & Applied Microbiology
John J. Cole, Neil A. Robertson, Mohammed Iqbal Rather, John P. Thomson, Tony McBryan, Duncan Sproul, Tina Wang, Claire Brock, William Clark, Trey Ideker, Richard R. Meehan, Richard A. Miller, Holly M. Brown-Borg, Peter D. Adams
Article
Immunology
A. A. Roger Thompson, Rebecca S. Dickinson, Fiona Murphy, John P. Thomson, Helen M. Marriott, Adriana Tavares, Joseph Willson, Lynne Williams, Amy Lewis, Ananda Mirchandani, Patricia Dos Santos Coelho, Catherine Doherty, Eilise Ryan, Emily Watts, Nicholas M. Morton, Shareen Forbes, Roland H. Stimson, Abdul G. Hameed, Nadine Arnold, Julie A. Preston, Allan Lawrie, Veronica Finisguerra, Massimiliano Mazzone, Pranvera Sadiku, Jermaine Goveia, Federico Taverna, Peter Carmeliet, Simon J. Foster, Edwin R. Chilvers, Andrew S. Cowburn, David H. Dockrell, Randall S. Johnson, Richard R. Meehan, Moira K. B. Whyte, Sarah R. Walmsley
SCIENCE IMMUNOLOGY
(2017)
Article
Biotechnology & Applied Microbiology
Colm E. Nestor, Raffaele Ottaviano, Diana Reinhardt, Hazel A. Cruickshanks, Heidi K. Mjoseng, Rhoanne C. McPherson, Antonio Lentini, John P. Thomson, Donncha S. Dunican, Sari Pennings, Stephen M. Anderton, Mikael Benson, Richard R. Meehan