Review
Biochemistry & Molecular Biology
Yuri Y. Shevelyov, Sergey Ulianov, Mikhail S. Gelfand, Stepan N. Belyakin, Sergey Razin
Summary: Dosage compensation ensures equal gene expression between a single male X chromosome and the pairs of autosomes and female X chromosomes. In fruit flies, canonical dosage compensation is achieved through the action of the male-specific lethal (MSL) complex in all male somatic cells. This complex contains the acetyl transferase males absent on the first (MOF), which specifically hyperacetylates H4K16 on the male X chromosome, promoting transcription of X-linked genes. Additionally, there is growing evidence for the existence of non-canonical dosage compensation mechanisms in somatic and germline cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Shuai Zhang, Haizhu Qi, Cheng Huang, Lijia Yuan, Ludan Zhang, Ruixue Wang, Yu Tian, Lin Sun
Summary: The study demonstrates that the inverse dosage effect caused by chromosome number variations has global consequences in genomic imbalance, including sexual dimorphism and an X chromosome-specific response. Over-expression of MSL2 and analysis of different transcriptomes revealed that the de novo MSL complex assembled on the X chromosomes in females further reduces global gene expression levels through epigenetic modulations.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Henrik Lindehell, Alexander Glotov, Eshagh Dorafshan, Yuri B. Schwartz, Jan Larsson
Summary: This study investigated the role of H3K36 methylation and associated methyltransferases in balancing transcriptional output in two chromosome-specific systems in Drosophila. The findings suggest that Set2, NSD, and Ash1 play important roles in maintaining transcriptional balance on the male X chromosome and chromosome 4.
Article
Multidisciplinary Sciences
Charles Limouse, Owen K. Smith, David Jukam, Kelsey A. Fryer, William J. Greenleaf, Aaron F. Straight
Summary: This study provides insights into the global network of interactions between non-coding RNAs (ncRNAs) and chromatin in human embryonic stem cells. The researchers find that ncRNAs predominantly interact with genes in close three-dimensional proximity to their encoding loci. They also identify numerous unannotated RNAs that dynamically interact with chromatin. The study suggests that activation or repression of individual genes is unlikely to be controlled by a single ncRNA.
NATURE COMMUNICATIONS
(2023)
Review
Multidisciplinary Sciences
Marc A. J. Morgan, Ali Shilatifard
Summary: In the past three decades, research on chromatin has provided valuable information about the mechanisms that regulate transcription. The histone code hypothesis has guided this research and uncovered fundamental mechanisms relevant to biology. Recent studies have shown that histone-modifying enzymes have noncatalytic functions beyond their enzymatic activities. This review highlights the latest advances in understanding these noncatalytic functions and calls for further research to explore the epigenetic moonlighting functions of chromatin-modifying enzymes.
Article
Biochemistry & Molecular Biology
Nikolas Eggers, Peter B. Becker
Summary: Using a unique experimental system, this study explored the principles of DNA shape recognition and factor cooperativity in chromatin. By reconstituting chromatin on Drosophila genomes, the researchers identified the physiological binding profile of MSL2 through interaction with other factors and competition with non-functional sites. The results revealed novel aspects of target selection in a complex chromatin environment.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Peiwei Chen, Alexei A. Aravin
Summary: This study revealed that the sexual dimorphism in piRNA program in Drosophila is mainly determined by germ cells rather than somatic cells. The presence of Y chromosome can partially replicate the male piRNA program in a female cellular environment, while sexual identity controls sexually divergent piRNA production by regulating Sxl, Phf7 and Kipferl. This work delineates the genetic control of sex-specific piRNA program.
Editorial Material
Biochemistry & Molecular Biology
Takashi Sado
Summary: The study shows that a subset of X-linked immune genes are repressed on the inactive X chromosome in B cells in a manner dependent on XIST RNA, and the derepression of these genes upon XIST depletion may bias the differentiation of naive B cells and be involved in the etiology of female-biased autoimmune diseases.
Article
Genetics & Heredity
William Jordan, Erica Larschan
Summary: In this study, it was demonstrated that CLAMP promotes the three-dimensional clustering of MSLc binding sites. Additionally, the X-enriched CLAMP protein was found to promote longer-range three-dimensional interactions on the X-chromosome more strongly than on autosomes. Genome-wide, CLAMP is shown to facilitate three-dimensional interactions between active chromatin regions along with other insulator proteins.
EPIGENETICS & CHROMATIN
(2021)
Article
Chemistry, Medicinal
Francesco Fiorentino, Sara Sementilli, Martina Menna, Federica Turrisi, Stefano Tomassi, Francesca Romana Pellegrini, Angela Iuzzolino, Francesca D'Acunzo, Alessandra Feoli, Hannah Wapenaar, Sophie Taraglio, Caterina Fraschetti, Donatella Del Bufalo, Gianluca Sbardella, Frank J. Dekker, Alessandro Paiardini, Daniela Trisciuoglio, Antonello Mai, Dante Rotili
Summary: KAT8, a lysine acetyltransferase, is involved in the development and metastasis of various cancer types. Two newly developed compounds, 19 and 34, are selective KAT8 inhibitors with low-micromolar activity and show antiproliferative effects in cancer cell lines, while not affecting nontransformed cells. These compounds provide valuable tools for studying KAT8 biology and have potential for further optimization studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Lidice Gonzalez, Daniel Kolbin, Christian Trahan, Celia Jeronimo, Francois Robert, Marlene Oeffinger, Kerry Bloom, Stephen W. Michnick
Summary: This study reveals that partitioning of active gene loci to the nuclear envelope occurs through phase separation of transcriptionally active chromatin, allowing for efficient mRNA transport and memory. This mechanism contributes to the speed of adaptation and metabolic robustness of organisms to fluctuating resources in the environment. Understanding the process of gene localization sheds light on gene regulation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Bingfei Yu, Yanyan Qi, Rui Li, Quanming Shi, Ansuman T. Satpathy, Howard Y. Chang
Summary: Research shows that XIST plays a continuous role in female B cells, silencing a subset of immune genes on the X chromosome. Genes dependent on XIST require continual histone deacetylation, and dysregulation of XIST in CD11c(+) atypical memory B cells may contribute to certain diseases.
Review
Cell Biology
Luisa Statello, Chun-Jie Guo, Ling-Ling Chen, Maite Huarte
Summary: Recent studies have shed new light on the biogenesis and functions of long non-coding RNAs (lncRNAs), showcasing their diverse roles in gene regulation and signaling pathways, particularly in the contexts of neuronal disorders, immune responses, and cancer. The discovery of unique biogenesis pathways and subcellular localizations of lncRNAs has opened up potential therapeutic avenues for targeting lncRNAs in various biological and pathophysiological conditions.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Article
Cell Biology
Alexandre Segelle, Yaiza Nunez-Alvarez, Andrew J. Oldfield, Kimberly M. Webb, Philipp Voigt, Reini F. Luco
Summary: Histone modifications play a role in final splicing decisions. In this study, researchers used CRISPR epigenome editing tools and found that a single change in H3K27ac or H3K27me3 levels at the alternatively spliced exon is sufficient to induce splicing changes associated with epithelial-to-mesenchymal transition (EMT). These findings suggest that the dynamic nature of chromatin and its histone marks can rapidly and reversibly regulate alternative splicing in response to cell-extrinsic cues like EMT induction.
Article
Chemistry, Medicinal
Katherine L. Jones, Dominic M. Beaumont, Sharon G. Bernard, Rino A. Bit, Simon P. Campbell, Chun-wa Chung, Leanne Cutler, Emmanuel H. Demont, Kate Dennis, Laurie Gordon, James R. Gray, Michael Haase, Antonia J. Lewis, Scott McCleary, Darren J. Mitchell, Susanne M. Moore, Nigel Parr, Olivia J. Robb, Nicholas Smithers, Peter E. Soden, Colin J. Suckling, Simon Taylor, Ann L. Walker, Robert J. Watson, Rab K. Prinjha
Summary: This study details the optimization process of the in vivo tool molecule I-BET151 towards I-BET282E, a molecule with properties suitable for clinical progression, in order to reduce the risk of compound attrition due to related toxicity findings.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Jeffrey J. Quinn, Qiangfeng C. Zhang, Plamen Georgiev, Ibrahim A. Ilik, Asifa Akhtar, Howard Y. Change
GENES & DEVELOPMENT
(2016)
Article
Cell Biology
Ibrahim Avsar Ilik, Daniel Maticzka, Plamen Georgiev, Noel Marie Gutierrez, Rolf Backofen, Asifa Akhtar
GENES & DEVELOPMENT
(2017)
Article
Multidisciplinary Sciences
Tugce Aktas, Ibrahim Avsar Ilik, Daniel Maticzka, Vivek Bhardwaj, Cecilia Pessoa Rodrigues, Gerhard Mittler, Thomas Manke, Rolf Backofen, Asifa Akhtar
Article
Multidisciplinary Sciences
Daniel Maticzka, Ibrahim Avsar Ilik, Tugce Aktas, Rolf Backofen, Asifa Akhtar
NATURE COMMUNICATIONS
(2018)
Article
Cell Biology
Thomas Conrad, Florence M. G. Cavalli, Herbert Holz, Erinc Hallacli, Jop Kind, Ibrahim Ilik, Juan M. Vaquerizas, Nicholas M. Luscombe, Asifa Akhtar
DEVELOPMENTAL CELL
(2012)
Article
Biochemistry & Molecular Biology
Ibrahim Avsar Ilik, Jeffrey J. Quinn, Plamen Georgiev, Filipe Tavares-Cadete, Daniel Maticzka, Sarah Toscano, Yue Wan, Robert C. Spitale, Nicholas Luscombe, Rolf Backofen, Howard Y. Chang, Asifa Akhtar
Article
Biotechnology & Applied Microbiology
Jeffrey J. Quinn, Ibrahim A. Ilik, Kun Qu, Plamen Georgiev, Ci Chu, Asifa Alchtar, Howard Y. Chang
NATURE BIOTECHNOLOGY
(2014)
Meeting Abstract
Hematology
Thomas Clapes, Aikaterini Polyzou, Pia Prater, Sagar Sagar, Barbara Hummel, Daniel Maticzka, Stylianos Lefkopoulos, Ibrahim Ilik, Lheanna Klaeyle, Rolf Backofen, Asifa Akhtar, Ritwick Sawarkar, Dominic Grun, Eirini Trompouki
Article
Biochemistry & Molecular Biology
Ibrahim Avsar Ilik, Tugce Aktas, Daniel Maticzka, Rolf Backofen, Asifa Akhtar
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biology
Ibrahim Avsar Ilik, Michal Malszycki, Anna Katharina Luebke, Claudia Schade, David Meierhofer, Tugce Aktas
Review
Biochemistry & Molecular Biology
Ibrahim Avsar Ilik, Tugce Aktas
Summary: Complex biochemical reactions in cells are facilitated by compartmentalization within organelles or membrane-less bodies to ensure efficiency and specificity. The nucleus, as one of the earliest discovered organelles, contains various membrane-less bodies. Recent research focuses on the formation of nuclear speckles (NS) and the role of specific proteins such as SON and SRRM2.
