Article
Biochemistry & Molecular Biology
Daniel S. Saxton, Jasper Rine
Summary: Genetically identical cells can have different transcriptional states. Inheritance of silenced states relies not only on the inheritance of modified histones, but also on the presence of silencers. Strong silencers recruit Sir proteins and silence the locus in all cells, while weakening silencers can result in stable silencing in some cells but with a probability of conversion to an expressed state lacking Sir protein recruitment. The presence of different silencer states and variations in silencer-bound proteins or the concentration of a structural Sir protein can modulate the probability of a locus exhibiting the silenced or expressed state.
Article
Biochemistry & Molecular Biology
Matthew P. Swaffer, Georgi K. Marinov, Huan Zheng, Lucas Fuentes Valenzuela, Crystal Yee Tsui, Andrew W. Jones, Jessica Greenwood, Anshul Kundaje, William J. Greenleaf, Rodrigo Reyes-Lamothe, Jan M. Skotheim
Summary: A fundamental feature of cellular growth is that protein and RNA amounts increase with cell size to maintain constant concentrations. In budding yeast, RNA polymerase II (RNAPII) is identified as the limiting factor scaling mRNA transcription with cell size. The global RNAPII transcription is determined by the mass action recruitment kinetics of unengaged nucle-oplasmic RNAPII to the genome. However, this increase in transcription with size is partially compensated for by a decrease in mRNA decay rates as cells enlarge.
Article
Plant Sciences
Hasan Mehraj, Satoshi Takahashi, Naomi Miyaji, Ayasha Akter, Yutaka Suzuki, Motoaki Seki, Elizabeth S. Dennis, Ryo Fujimoto
Summary: Covalent modifications of histone proteins, such as H3K4me3 and H3K36me3, are found to regulate gene expression in Brassica rapa L. Two lines of this species showed enrichment of these histone marks at transcription start sites, with gene expression levels being influenced by them. Genes with both H3K4me3 and H3K36me3 typically showed constitutive high expression levels. Additionally, bivalent active and repressive histone modifications were observed in some genes.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Masaki Kikuchi, Satoshi Morita, Mie Goto, Masatoshi Wakamori, Kazushige Katsura, Kazuharu Hanada, Mikako Shirouzu, Takashi Umehara
Summary: In this study, the researchers established a nucleosome core particle (NCP) array containing histones with specific acetylated residues and compared the Kac-binding preferences of human YEATS domains. They found that the Kac-binding affinity of AF9-YEATS increased with the number of acetylated residues in the histone tail.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Masaki Kikuchi, Satoshi Morita, Mie Goto, Masatoshi Wakamori, Kazushige Katsura, Kazuharu Hanada, Mikako Shirouzu, Takashi Umehara
Summary: In this study, AF9-YEATS was found to have differential binding preferences for specific Kac positions and multiple Kac in histone H3. Crystal structures revealed that the aromatic cage of AF9-YEATS recognized the acetylated K8 residue, while E57 and D103 outside of the aromatic cage interacted with acetylated K5 and K12. Additionally, mutating E57 to alanine reduced the binding affinity of AF9-YEATS for multiacetylated H4.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kevin E. W. Namitz, Song Tan, Michael S. Cosgrove
Summary: In this study, the biophysical properties of a reconstituted human MLL1 core complex were characterized. It was found that the MLL1-WDR5 heterodimer interacts with the RbBP5-Ash2L-DPY30 subcomplex in a hierarchical assembly pathway that is highly dependent on concentration and temperature. Surprisingly, the disassembled state is favored at physiological temperature, leading to irreversible inactivation of the enzyme.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Plant Sciences
Huihui Fang, Yuke Shao, Gang Wu
Summary: This review discusses the reprogramming of histone H3 methylation during plant sexual reproduction, highlighting its importance in cell specification and establishment of pluripotency. Despite advancements in understanding this process, challenges remain in this area and future breakthroughs in cell-specific epigenomic profiling are expected to provide a solution.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Multidisciplinary Sciences
Fei He, Qi Yu, Min Wang, Rongsha Wang, Xuanyunjing Gong, Feng Ge, Xilan Yu, Shanshan Li
Summary: This study reveals the inhibitory effect of H3pT11 on H3K79me3 and uncovers the histone crosstalk regulating autophagy and telomere silencing. It is also discovered that Reb1 recruits the SESAME complex to telomere regions to prevent the invasion of H3K79me3 into heterochromatin, maintaining telomere silencing.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Francesco Abbiati, Stefano Angelo Garagnani, Ivan Orlandi, Marina Vai
Summary: Supplementation of Quercetin (QUER) in yeast cells can increase their lifespan by reducing oxidative stress and promoting anabolic metabolism, specifically gluconeogenesis, leading to an increase in trehalose, a reserve carbohydrate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Yeong Hyeock Kim, Ji-In Ryu, Mayur Nimbadas Devare, Juhye Jung, Jeong-Yoon Kim
Summary: This study investigated the molecular mechanism underlying the altered stress susceptibilities in Saccharomyces cerevisiae due to the absence of Sir2. The absence of Sir2 increased sensitivity to H2O2 during the post-diauxic phase but increased resistance during the exponential growth phase. Transcriptome analysis revealed lower expression levels of several oxidative defense genes in the sir2 Delta strain, potentially explaining its increased susceptibility to H2O2. Interestingly, the sir2 Delta ras2 Delta double mutant exhibited greater resistance to H2O2 than the ras2 Delta single mutant, and the regulation of the cytoplasmic catalase encoded by CTT1 was critical for this increased resistance.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biology
Qianyun Mei, Qi Yu, Xin Li, Jianguo Chen, Xilan Yu
Summary: Histone loss during yeast aging compromises telomere silencing by promoting Sir2 degradation through autophagy. Reduction of core histones enhances autophagy pathway, further accelerating autophagy-mediated Sir2 degradation. Screening of histone mutants and one histone modification identifies regulators of telomere silencing via modulation of core histones-autophagy-Sir2 axis.
LIFE SCIENCE ALLIANCE
(2023)
Article
Multidisciplinary Sciences
Shihao Zhang, Xilan Yu, Yuan Zhang, Xiangyan Xue, Qi Yu, Zitong Zha, Madelaine Gogol, Jerry L. Workman, Shanshan Li
Summary: Telomeres, organized into heterochromatin, require maintenance of silent heterochromatin for chromosome stability. The study shows that Pyruvate kinase Pyk1 phosphorylates histone H3T11 and regulates gene expression through the SESAME complex. SESAME phosphorylates H3T11 at telomeres to maintain SIR complex occupancy and prevent autophagy-mediated Sir2 degradation, ultimately enhancing telomere silencing and protecting against compromised telomere silencing during aging.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Meagan Jezek, Winny Sun, Maraki Y. Negesse, Zachary M. Smith, Alexander Orosz, Erin M. Green
Summary: Set1 is an H3K4 methyltransferase involved in various genomic functions. It plays a role in subtelomeric gene repression through its catalytic activity towards H3K4 and regulates telomere length through its catalytic activity but likely independent of the H3K4 substrate. Set1 also calibrates the abundance of critical telomere maintenance proteins through transcriptional and posttranscriptional pathways. These findings provide new insights into the roles of Set1 in telomere maintenance and have implications for Set1-related methyltransferases in other systems.
MOLECULAR BIOLOGY OF THE CELL
(2023)
Article
Biochemistry & Molecular Biology
Bo Bae Lee, Hyeonju Woo, Min Kyung Lee, SeoJung Youn, Sumin Lee, Jae-Seok Roe, Soo Young Lee, TaeSoo Kim
Summary: Chromatin-based regulation of internal cryptic promoters is mediated by core promoter strength as well as transcription elongation factors.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Genetics & Heredity
Stefanie L. Bauer, Thomas N. T. Grochalski, Agata Smialowska, Stefan U. Astrom
Summary: Telomere chromatin structure is crucial for maintaining genome stability. In this study, the authors discovered that the Silent information regulator protein Sir2 and the transcription factor Reb1 play important roles in regulating telomere chromatin structure and repressing telomeric-repeat-containing RNAs (TERRAs). They found that Sir2 and Reb1 compete for stabilizing/destabilizing a nucleosome in the X-elements and act in different pathways for repressing TERRAs.
Review
Biochemistry & Molecular Biology
Cynthia Wolberger
Summary: Over the past four decades, significant progress has been made in our understanding of the structural basis of gene regulation, thanks to technological advances in protein expression, nucleic acid synthesis, and structural biology. This review focuses on insights gained from structural studies of protein-DNA complexes and the role the Protein Data Bank has played in driving this research. From X-ray crystal structures to recent cryo-EM structures, the highlights of the field are covered, detailing the study of transcription factors binding to nucleosomal DNA.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Multidisciplinary Sciences
Vera Gorbunova, Andrei Seluanov, Paolo Mita, Wilson McKerrow, David Fenyo, Jef D. Boeke, Sara B. Linker, Fred H. Gage, Jill A. Kreiling, Anna P. Petrashen, Trenton A. Woodham, Jackson R. Taylor, Stephen L. Helfand, John M. Sedivy
Summary: The article discusses the impact of transposons on aging and age-related diseases in complex metazoan organisms, focusing on the activity of retrotransposons in particular. Research has shown that the activity of retrotransposons in somatic tissues during an individual's lifespan influences health and well-being, intersecting with our own physiology.
Article
Multidisciplinary Sciences
Wilson McKerrow, Xuya Wang, Carlos Mendez-Dorantes, Paolo Mita, Song Cao, Mark Grivainis, Li Ding, John LaCava, Kathleen H. Burns, Jef D. Boeke, David Fenyo
Summary: LINE-1, an active retrotransposon, is derepressed in many cancers and is correlated with p53 mutation and copy number alteration. It induces replication stress and is associated with the DNA damage response pathway in endometrial cancer.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Aaron N. Brooks, Amanda L. Hughes, Sandra Clauder-Muenster, Leslie A. Mitchell, Jef D. Boeke, Lars M. Steinmetz
Summary: This study investigates the effects of sequence features and transcriptional context on RNA transcript isoform expression. Using synthetic yeast strains with rearranged genes, the researchers discovered that neighboring transcription also influences gene expression levels and transcript isoform boundaries. They identified features of transcriptional context that can predict these alterations and successfully engineered a synthetic circuit where transcript length is controlled by neighboring transcription.
Article
Multidisciplinary Sciences
Weimin Zhang, Ran Brosh, Laura H. McCulloch, Yinan Zhu, Hannah Ashe, Gwen Ellis, Brendan R. Camellato, Sang Yong Kim, Matthew T. Maurano, Jef D. Boeke
Summary: This study presents a new conditional knockout strategy that enables efficient counter selection in mouse embryonic stem cells. The strategy overwrites counter selectable markers and allows the removal or replacement of wild-type DNA with the desired payload DNA. The restored native gene function in the conditional knockout cells facilitates subsequent mouse development and the generality of the strategy is demonstrated through the knockout of other genes.
Article
Multidisciplinary Sciences
Sanim Rahman, Niklas A. Hoffmann, Evan J. Worden, Marissa L. Smith, Kevin E. W. Namitz, Bruce A. Knutson, Michael S. Cosgrove, Cynthia Wolberger
Summary: This study determines the structure of the MLL1-WRAD complex bound to ubiquitinated nucleosomes using an integrated approach. The structure reveals the conformation of Ash2L's intrinsically disordered region, SPRY insertion region, Sdc1-DPY30 interacting region, and DPY30 dimer. The study also uncovers different states of MLL1-WRAD during its assembly. The docking of subunits in the complex differs when bound to ubiquitinated nucleosomes, indicating the role of ubiquitin in promoting the formation of the active complex.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Wilson McKerrow, Larisa Kagermazova, Nicole Doudican, Nicholas Frazzette, Efiyenia Ismini Kaparos, Shane A. Evans, Azucena Rocha, John M. Sedivy, Nicola Neretti, John Carucci, Jef D. Boeke, David Fenyo
Summary: LINE-1 retrotransposons are sequences capable of copying themselves to new genomic loci via an RNA intermediate. New studies using the method-5 ' scL1seq have identified LINE-1 expression in human epithelial cells and mouse hippocampal neurons, in addition to its known expression in tumors. The findings also suggest a modest increase in LINE-1 expression with age, supporting its association with age-related diseases.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yu Zhao, Camila Coelho, Stephanie Lauer, Milosz Majewski, Jon M. Laurent, Ran Brosh, Jef D. Boeke
Summary: The use of synthetic genomics has revolutionized our ability to answer fundamental biological questions by designing and building "big" DNA constructs. Saccharomyces cerevisiae, or budding yeast, is a powerful platform for assembling large synthetic constructs, but introducing designer variations to episomal assemblies remains challenging. The CRISPR Engineering of EPisomes in Yeast (CREEPY) method provides a rapid and efficient way to edit large synthetic episomal DNA constructs.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Makiha Fukuda, Jitong Cai, Joel S. Bader, Jef D. Boeke
Summary: A synthetic biology approach to constructing an RNA-based genome expands our understanding of living things and opens avenues for technological advancement. Understanding the structure-function relationships of RNA sequences is critical for the precise design of an artificial RNA replicon.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Srinjoy Sil, Sarah Keegan, Farida Ettefa, Lance T. Denes, Jef D. Boeke, Liam J. Holt
Summary: LINE-1 (L1) is the dominant retrotransposon in the human genome, accounting for 17% of the genome. The condensation of ORF1p, a RNA-binding protein encoded by L1, is critical for efficient L1 retrotransposition. By studying the assembly dynamics and material properties of ORF1p, we propose that dynamic oligomerization of ORF1p on L1 RNA drives the formation of an essential L1 ribonucleoprotein (RNP) condensate for retrotransposition.
Article
Biochemistry & Molecular Biology
James K. Fields, Chad W. Hicks, Cynthia Wolberger
Summary: Post-translational modification of histones, including methylation and monoubiquitination, plays a crucial role in transcription regulation. Methylation of H3K4 and H3K79 activates transcription, while methylation of H3K27 represses transcription. These modifications are dependent on prior monoubiquitination of specific histone residues, leading to a phenomenon called histone crosstalk. Recent studies have provided new insights into the mechanisms of how these modifications regulate the activity of various histone-modifying enzymes.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Neurosciences
Paul W. Frazel, David Labib, Theodore Fisher, Ran Brosh, Nicolette Pirianian, Anne Marchildon, Jef D. Boeke, Valentina Fossati, Shane A. Liddelow
Summary: Researchers used single-cell/single-nucleus RNA sequencing to analyze the differentiation of macroglia in the brain and spinal cord. They identified candidate genes involved in glial cell fate specification and observed heterogeneous expression of astrocyte surface markers during differentiation. The researchers also optimized a mouse astrocyte differentiation protocol and explored potential genomic regulatory sites mediating glial differentiation using multi-omic analysis.
NATURE NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Fan Zhao, Chad W. Hicks, Cynthia Wolberger
Summary: This study reveals the mechanism by which the E3 ligase Bre1 directs monoubiquitination of histone H2B at K123 by the E2 ubiquitin-conjugating enzyme Rad6, and compares the roles of other dimeric E3 ligases, suggesting a mechanism of tuning histone residue specificity.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Genetics & Heredity
Guojon Olafsson, Max A. B. Haase, Jef D. Boeke
Summary: This study demonstrates that the differences in protein composition from different species may lead to complementation failure during mitosis.
G3-GENES GENOMES GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Michael Morgan, Tatsuya Ikenoue, Hiroaki Suga, Cynthia Wolberger
Summary: The Spt-Ada-Gcn5 acetyltransferase (SAGA) transcriptional coactivator contains a subcomplex called the deubiquitinating enzyme (DUB) module that can remove ubiquitin from histone H2B-K120. The human DUB module includes the catalytic subunit ubiquitin-specific protease 22 (USP22), which is overexpressed in certain cancers resistant to existing therapies. By screening a large library of cyclic peptides, potent inhibitors of USP22 were identified. The top hit showed high specificity for USP22 and was able to enter human cells and inhibit H2B deubiquitination.
CELL CHEMICAL BIOLOGY
(2022)