Article
Multidisciplinary Sciences
Marco Igor Valencia-Sanchez, Pablo De Ioannes, Miao Wang, David M. Truong, Rachel Lee, Jean-Paul Armache, Jef D. Boeke, Karim-Jean Armache
Summary: This study demonstrates that acetylation of histone H4 can stimulate the activity of yeast Dot1 in a specific manner, which coordinates with histone H2B ubiquitination to affect H3K79 methylation. H4K16ac and H2BUb play crucial roles in histone cross-talk, regulating gene transcription and gene silencing together.
Article
Multidisciplinary Sciences
Jimin Li, Jingyu Zhao, Xiaoli Gan, Yanyan Wang, Donghao Jiang, Liang Chen, Fangwei Wang, Jingyan Xu, Huadong Pei, Jun Huang, Xuefeng Chen
Summary: The interaction between the single-strand DNA-binding factor Replication protein A (RPA) and Ring finger protein 20 (RNF20) is important for chromosome segregation and DNA repair. RPA recruits RNF20 to mitotic centromeres and chromosomal breaks, leading to proper loading of repair proteins and maintenance of genome stability. The RPA-RNF20-SNF2H cascade plays a crucial role in preserving genome stability by coupling histone modification to chromosome segregation and DNA repair.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Prajakta Tathe, K. V. S. Rammohan Chowdary, Krushna Chandra Murmu, Punit Prasad, Subbareddy Maddika
Summary: In this study, the researchers discovered that the tyrosine phosphatase SHP-1 can dephosphorylate histone H2B and plays a critical role in transcription. SHP-1 dephosphorylates H2B at tyrosine 121, promoting H2B ubiquitination and maintaining basal autophagic flux. This study reveals the importance of SHP-1-regulated modification of H2B in eukaryotic transcription.
Article
Plant Sciences
Zuntao Xu, Enze Li, Gan Xue, Cheng Zhang, Yachun Yang, Yong Ding
Summary: This study reveals that OsHUB2 represses the function of OsTrx1 and H3K4me3 levels at Ehd1, and suggests that OsHUB2-mediated H2B ubiquitination plays critical roles together with H3K4me3 in rice heading date regulation.
Article
Cell Biology
Yu -Min Li, Yu -Chao Mei, Ao-Hui Liu, Ru-Xin Wang, Runfa Chen, Hai-Ning Du
Summary: Loss of H3K36me3 during aging is caused by the degradation of Set2 through the actions of Ubc3 and Bre1. Lack of Bre1 or removal of ubiquitination stabilizes Set2, sustains H3K36me3 levels, and extends lifespan.
Article
Biochemistry & Molecular Biology
Fengling Lai, Yibin Cheng, Juan Zou, Haoyu Wang, Wang Zhu, Xin Wang, Hanhua Cheng, Rongjia Zhou
Summary: This study examined histone modifications in gonadal differentiation, identifying new modification sites and their relationship with different types of gonadal differentiation. The research also discovered a testis-enriched histone modification site associated with spermatogenesis, emphasizing the importance of histone modifications in the transcriptional regulation of sex-determining genes during gonadal development.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Oncology
Lucile M. Jeusset, Kirk J. McManus
Summary: Monoubiquitination of histone H2B on lysine 120 plays a crucial role in various biological processes. Aberrant regulation of H2Bub1 can lead to transcriptional reprogramming and genome instability, thereby promoting oncogenesis. Understanding the misregulation of H2Bub1 may reveal novel drug targets and therapeutic strategies for cancer treatment.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Guangxue Liu, Jiaqi Yan, Xuejie Wang, Junliang Chen, Xin Wang, Yang Dong, Simin Zhang, Xiaoli Gan, Jun Huang, Xuefeng Chen
Summary: The study reveals that the ssDNA binding factor RPA mediates the coupling of Bre1-mediated H2Bub with DNA replication and repair processes, ensuring the proper functioning of H2Bub in these contexts. Disruption of the interaction between RPA and Bre1 leads to instability of H2Bub, affecting DNA replication, repair, and genome stability.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Zhiheng Deng, Huasong Ai, Maoshen Sun, Zebin Tong, Yunxiang Du, Qian Qu, Liying Zhang, Ziyu Xu, Shixian Tao, Qiang Shi, Jia-Bin Li, Man Pan, Lei Liu
Summary: This study elucidates the mechanism of H2B monoubiquitylation and highlights the critical role of nucleosomal DNA in mediating E3 ligase recognition.
Article
Cell Biology
Jianfeng Wang, Yutao Wang, Jianbin Bi
Summary: The study revealed that INMT is downregulated in prostate cancer and significantly correlated with lymph node metastasis, Gleason score, PSA expression, and survival. INMT is involved in regulating multiple signaling pathways and affects tumor microenvironments and immune cell proportions, influencing the development and drug sensitivity of prostate cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Shinya Takahata, Saori Chida, Aoi Ohnuma, Motoyoshi Ando, Takahiro Asanuma, Yota Murakami
Summary: In heterochromatin, Spt16 recruitment is mediated by Pob3 and HP1/Swi6. Pob3 recruits Spt16 through its Spt16 dimerization and PH domains, while HP1/Swi6 recruits Spt16 through physical interaction of the Swi6 CSD and Spt16 peptidase-like domains.
Article
Oncology
Wei Sun, Yongjia Jin, Chuanyuan Wei, Yu Xu, Wanlin Liu, Jingqin Zhong, Zijian Zou, Xinyi Lin, Yang Xiang, Yong Chen
Summary: CDCA2 is highly expressed in melanoma and enhances the stability of AURKA protein by inhibiting SMAD specific E3 ubiquitin protein ligase 1-mediated AURKA ubiquitination, thus playing a carcinogenic role in melanoma progression.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Cell Biology
Longxiang Wu, Zhenyu Ou, Peihua Liu, Cheng Zhao, Shiyu Tong, Ruizhe Wang, Yangle Li, Junbin Yuan, Minfeng Chen, Benyi Fan, Xiongbing Zu, Yongjie Wang, Jianing Tang
Summary: In this study, ATXN3 was identified as a deubiquitinating enzyme of YAP in prostate cancer. It interacted with YAP and inhibited the K48-specific poly-ubiquitination of YAP, thus stabilizing YAP protein and promoting the proliferation, invasion, and stem-like properties of prostate cancer cells. These findings provide a potential target for the therapy of prostate cancer.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Oncology
Yongwen Luo, Jun Zhou, Jianing Tang, Fengfang Zhou, Zhiwen He, Tongzu Liu, Tao Liu
Summary: This study identified MINDY1 as a deubiquitinating enzyme of YAP in bladder cancer, demonstrating its role in interacting with, deubiquitinating, and stabilizing YAP. Depletion of MINDY1 led to decreased cell proliferation in bladder cancer, which could be rescued by YAP overexpression, affecting the expression of YAP and its target genes.
CANCER CELL INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Yueke Lin, Xiaoting Lv, Caiyu Sun, Yanlin Sun, Min Yang, Dapeng Ma, Weiqiang Jing, Yunxue Zhao, Yeping Cheng, Haocheng Xuan, Lihui Han
Summary: This study reveals a novel regulatory mechanism of NLRP3 via TRIM50 and suggests that modulating TRIM50 might represent a therapeutic strategy for NLRP3-dependent pathologies.
Article
Biochemistry & Molecular Biology
Ioannis Tsirkas, Daniel Dovrat, Manikandan Thangaraj, Ineke Brouwer, Amit Cohen, Zohar Paleiov, Michael M. Meijler, Tineke Lenstra, Amir Aharoni
Summary: The coexistence of DNA replication and transcription during S-phase requires tight coordination to prevent conflicts. This study developed a live-cell imaging approach to monitor the real-time progression of replisomes and transcription dynamics during a transcription-replication encounter. The findings showed a wave of partial transcriptional repression ahead of the moving replication fork, and revealed the negative impact of conflicts on both processes.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Thom M. Molenaar, Fred van Leeuwen
Summary: Histone modifying enzymes have important roles in cellular processes and disease. SETD2, for example, methylates histone H3 on lysine 36 (H3K36) during transcription and also methylates non-histone substrates. Understanding the multiple roles of SETD2 is crucial for understanding its role in disease, particularly in cancer where it is frequently inactivated.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Hanneke Vlaming, Claudia A. Mimoso, Andrew R. Field, Benjamin J. E. Martin, Karen Adelman
Summary: This study reveals the importance of transcribed sequence in dictating gene output, with higher AT content in non-coding RNAs leading to RNAPII termination. Additionally, 5' splice sites can autonomously stimulate transcription.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Thom M. Molenaar, Muddassir Malik, Joana Silva, Ning Qing Liu, Judith H. Haarhuis, Christina Ambrosi, Eliza Mari Kwesi-Maliepaard, Tibor van Welsem, Tuncay Baubec, William J. Faller, Fred van Leeuwen
Summary: Cell size is tightly regulated and changes in cell size are frequently observed in cancer. In this study, we found that SETD2, a lysine methyltransferase protein, plays a role in regulating cell size by negatively regulating global protein synthesis rates. Overexpression of the H3K36 demethylase KDM4A or the oncohistone H3.3K36M also led to an increase in cell size, suggesting the importance of H3K36 methylation in cell size regulation.
JOURNAL OF CELL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Lingmin Yuan, Fei Gao, Zongyang Lv, Digant Nayak, Anindita Nayak, Priscila dos Santos Bury, Kristin E. Cano, Lijia Jia, Natalia Oleinik, Firdevs Cansu Atilgan, Besim Ogretmen, Katelyn M. Williams, Christopher Davies, Farid El Oualid, Elizabeth Wasmuth, Shaun K. Olsen
Summary: This article presents the crystal structures of Uba6, revealing its catalytic mechanisms and the modulatory role of inositol hexakisphosphate as a cofactor. The study shows that inositol hexakisphosphate allosterically inhibits Uba6 activity by altering the conformational interconversion and enhancing stability. The findings provide insights into the catalysis of Uba6 and the possibility of allosteric regulation of other E1 enzymes by cellular metabolites.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Lisa Willemsen, Koen H. M. Prange, Annette E. Neele, Cindy P. A. A. Van Roomen, Marion Gijbels, Guillermo R. Griffith, Myrthe Den Toom, Linda Beckers, Ricky Siebeler, Nathanael J. Spann, Hung-Jen Chen, Laura A. Bosmans, Andrej Gorbatenko, Suzanne Van Wouw, Noam Zelcer, Heinz Jacobs, Fred Van Leeuwen, Menno P. J. De Winther
Summary: This study reveals the crucial role of DOT1L in macrophages, showing its direct regulation of macrophage function through lipid regulatory pathways and inflammatory responses. DOT1L inhibition leads to macrophage hyperactivation and disruption of lipid metabolism, which have implications for the development of inflammatory diseases.
Article
Genetics & Heredity
Eliza Mari Kwesi-Maliepaard, Muddassir Malik, Tibor van Welsem, Remco van Doorn, Maarten H. Vermeer, Hanneke Vlaming, Heinz Jacobs, Fred van Leeuwen
Summary: The therapeutic effect of commonly used pan-HDAC inhibitors in CTCL cells may rely on downstream effects that are unrelated to the regulation of DOT1L.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Melina Blanco, Laila El Khattabi, Clara Gobe, Marion Crespo, Manon Coulee, Alberto de la Iglesia, Come Ialy-Radio, Clementine Lapoujade, Maelle Givelet, Marion Delessard, Ivan Seller-Corona, Kosuke Yamaguchi, Nadege Vernet, Fred Van Leeuwen, Alban Lermine, Yuki Okada, Romain Daveau, Rafael Oliva, Pierre Fouchet, Ahmed Ziyyat, Delphine Pflieger, Julie Cocquet
Summary: In this study, it is found that the H3K79-methyltransferase DOT1L plays a crucial role in spermatid chromatin remodeling and gene expression regulation. The knockout of the Dot1l gene in mice resulted in less compact chromatin structure and abnormal content in spermatozoa, including the presence of transition proteins, immature protamine 2 forms, and higher levels of histones. Additionally, the Dot1l knockout also caused less compact heads and decreased motility in spermatozoa, leading to impaired fertility.
Article
Biochemistry & Molecular Biology
Heta P. Patel, Stefano Coppola, Wim Pomp, Umberto Aiello, Ineke Brouwer, Domenico Libri, Tineke L. Lenstra
Summary: DNA supercoiling is a major factor in gene regulation in bacteria, but its impact on transcription dynamics in eukaryotes has been unclear. Single-molecule dual-color nascent transcription imaging in budding yeast reveals that transcriptional bursting of neighboring GAL genes is coupled. This coupling requires rapid release of DNA supercoils by topoisomerases. Accumulated supercoils inhibit transcription of adjacent genes by destabilizing the binding of the transcription factor Gal4. Wild-type yeast minimizes this inhibition by maintaining sufficient levels of topoisomerases, ensuring proper gene expression of neighboring genes.
Article
Biochemistry & Molecular Biology
Ineke Brouwer, Emma Kerklingh, Fred van Leeuwen, Tineke L. Lenstra
Summary: Using single-molecule live-cell imaging, Brouwer et al. investigate how the remodeling of promoter nucleosomes regulates transcriptional bursting. They find that at the Gal4 binding sites, RSC and Gal4 binding synergistically facilitate each burst. In contrast, nucleosome remodeling at the TATA box controls only the first burst upon galactose induction. The results reveal the importance of promoter nucleosome remodeling in regulating the kinetics of transcription.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Joseph V. W. Meeussen, Wim Pomp, Ineke Brouwer, Wim J. de Jonge, Heta P. Patel, Tineke L. Lenstra
Summary: The budding yeast TF Gal4 forms clusters that overlap with the GAL loci. Cluster number, density and size are regulated by the Gal4-inhibitor Gal80 and Gal4 concentration. Clustering aids TF recruitment to target genes, but non-DNA-bound Gal4 molecules inhibit transcription activation.
NUCLEIC ACIDS RESEARCH
(2023)