bims-crepig Biomed News
on Chromatin regulation and epigenetics in cell fate and cancer
Issue of 2023‒02‒26
seventeen papers selected by
Connor Rogerson
University of Cambridge
  1. Dynamic interplay between non-coding enhancer transcription and gene activity in development.
  2. Measuring Inaccessible Chromatin Genome-Wide Using Protect-seq.
  3. SETD2 regulates chromatin accessibility and transcription to suppress lung tumorigenesis.
  4. Extensive de novo activity stabilizes epigenetic inheritance of CG methylation in Arabidopsis transposons.
  5. MacroH2A histone variants modulate enhancer activity to repress oncogenic programs and cellular reprogramming.
  6. eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways.
  7. Single-Cell Joint Profiling of Open Chromatin and Transcriptome by Paired-Seq.
  8. Simultaneous Measurement of DNA Methylation and Nucleosome Occupancy in Single Cells Using scNOMe-Seq.
  9. PBRM1 bromodomains associate with RNA to facilitate chromatin association.
  10. Kinetic networks identify TWIST2 as a key regulatory node in adipogenesis.
  11. BAP18 facilitates CTCF-mediated chromatin accessible to regulate enhancer activity in breast cancer.
  12. Widespread perturbation of ETS factor binding sites in cancer.
  13. DNA-initiated epigenetic cascades driven by C9orf72 hexanucleotide repeat.
  14. Retrospective analysis of enhancer activity and transcriptome history.
  15. Comprehensive chromatin proteomics resolves functional phases of pluripotency and identifies changes in regulatory components.
  16. Enhancer activation via TCP and HD-ZIP and repression by Dof transcription factors mediate giant cell-specific expression.
  17. JMJ28 guides sequence-specific targeting of ATX1/2-containing COMPASS-like complex in Arabidopsis.
  1. Nat Commun. 2023 Feb 20. 14(1): 826
    Dynamic interplay between non-coding enhancer transcription and gene activity in development.
    Kota Hamamoto, Yusuke Umemura, Shiho Makino, Takashi Fukaya.
      Non-coding transcription at the intergenic regulatory regions is a prevalent feature of metazoan genomes, but its biological function remains uncertain. Here, we devise a live-imaging system that permits simultaneous visualization of gene activity along with intergenic non-coding transcription at single-cell resolution in Drosophila. Quantitative image analysis reveals that elongation of RNA polymerase II across the internal core region of enhancers leads to suppression of transcriptional bursting from linked genes. Super-resolution imaging and genome-editing analysis further demonstrate that enhancer transcription antagonizes molecular crowding of transcription factors, thereby interrupting the formation of a transcription hub at the gene locus. We also show that a certain class of developmental enhancers are structurally optimized to co-activate gene transcription together with non-coding transcription effectively. We suggest that enhancer function is flexibly tunable through the modulation of hub formation via surrounding non-coding transcription during development.
    DOI:  https://doi.org/10.1038/s41467-023-36485-1
  2. Methods Mol Biol. 2023 ;2611 53-61
    Measuring Inaccessible Chromatin Genome-Wide Using Protect-seq.
    George Spracklin, Liyan Yang, Sriharsa Pradhan, Job Dekker.
      Chromatin accessibility has been an immensely powerful metric for identifying and understanding regulatory elements in the genome. Many important regulatory elements, such as enhancers and transcriptional start sites, are characterized by "open" or nucleosome-free regions. Understanding the areas of the genome that are not considered open chromatin has been more difficult. Protect-seq is a genomics technique that aims to identify inaccessible chromatin associated with the nuclear periphery. These regions are enriched for histone modifications associated with transcriptional repression and correlate with loci identified by other techniques measuring heterochromatin and peripheral localization. Here, we discuss the protocol and best practices to perform Protect-seq.
    Keywords:  Chromatin; Genomics; Heterochromatin; Nuclear periphery; Protect-seq
    DOI:  https://doi.org/10.1007/978-1-0716-2899-7_4
  3. JCI Insight. 2023 Feb 22. pii: e154120. [Epub ahead of print]8(4):
    SETD2 regulates chromatin accessibility and transcription to suppress lung tumorigenesis.
    Yuchen Xie, Merve Sahin, Toru Wakamatsu, Akane Inoue-Yamauchi, Wanming Zhao, Song Han, Amrita M Nargund, Shaoyuan Yang, Yang Lyu, James J Hsieh, Christina S Leslie, Emily H Cheng.
      SETD2, a H3K36 trimethyltransferase, is the most frequently mutated epigenetic modifier in lung adenocarcinoma, with a mutation frequency of approximately 9%. However, how SETD2 loss of function promotes tumorigenesis remains unclear. Using conditional Setd2-KO mice, we demonstrated that Setd2 deficiency accelerated the initiation of KrasG12D-driven lung tumorigenesis, increased tumor burden, and significantly reduced mouse survival. An integrated chromatin accessibility and transcriptome analysis revealed a potentially novel tumor suppressor model of SETD2 in which SETD2 loss activates intronic enhancers to drive oncogenic transcriptional output, including the KRAS transcriptional signature and PRC2-repressed targets, through regulation of chromatin accessibility and histone chaperone recruitment. Importantly, SETD2 loss sensitized KRAS-mutant lung cancer to inhibition of histone chaperones, the FACT complex, or transcriptional elongation both in vitro and in vivo. Overall, our studies not only provide insight into how SETD2 loss shapes the epigenetic and transcriptional landscape to promote tumorigenesis, but they also identify potential therapeutic strategies for SETD2 mutant cancers.
    Keywords:  Epigenetics; Lung cancer; Oncology
    DOI:  https://doi.org/10.1172/jci.insight.154120
  4. Cell Rep. 2023 Feb 22. pii: S2211-1247(23)00143-2. [Epub ahead of print]42(3): 112132
    Extensive de novo activity stabilizes epigenetic inheritance of CG methylation in Arabidopsis transposons.
    David B Lyons, Amy Briffa, Shengbo He, Jaemyung Choi, Elizabeth Hollwey, Jack Colicchio, Ian Anderson, Xiaoqi Feng, Martin Howard, Daniel Zilberman.
      Cytosine methylation within CG dinucleotides (mCG) can be epigenetically inherited over many generations. Such inheritance is thought to be mediated by a semiconservative mechanism that produces binary present/absent methylation patterns. However, we show here that, in Arabidopsis thaliana h1ddm1 mutants, intermediate heterochromatic mCG is stably inherited across many generations and is quantitatively associated with transposon expression. We develop a mathematical model that estimates the rates of semiconservative maintenance failure and de novo methylation at each transposon, demonstrating that mCG can be stably inherited at any level via a dynamic balance of these activities. We find that DRM2-the core methyltransferase of the RNA-directed DNA methylation pathway-catalyzes most of the heterochromatic de novo mCG, with de novo rates orders of magnitude higher than previously thought, whereas chromomethylases make smaller contributions. Our results demonstrate that stable epigenetic inheritance of mCG in plant heterochromatin is enabled by extensive de novo methylation.
    Keywords:  Arabidopsis; CP: Molecular biology; CP: Plants; DDM1; DNA methylation; epigenetic inheritance; mathematical modeling; transposable elements
    DOI:  https://doi.org/10.1016/j.celrep.2023.112132
  5. Commun Biol. 2023 Feb 23. 6(1): 215
    MacroH2A histone variants modulate enhancer activity to repress oncogenic programs and cellular reprogramming.
    Wazim Mohammed Ismail, Amelia Mazzone, Flavia G Ghiraldini, Jagneet Kaur, Manvir Bains, Amik Munankarmy, Monique S Bagwell, Stephanie L Safgren, John Moore-Weiss, Marina Buciuc, Lynzie Shimp, Kelsey A Leach, Luis F Duarte, Chandandeep S Nagi, Saul Carcamo, Chi-Yeh Chung, Dan Hasson, Neda Dadgar, Jian Zhong, Jeong-Heon Lee, Fergus J Couch, Alexander Revzin, Tamas Ordog, Emily Bernstein, Alexandre Gaspar-Maia.
      Considerable efforts have been made to characterize active enhancer elements, which can be annotated by accessible chromatin and H3 lysine 27 acetylation (H3K27ac). However, apart from poised enhancers that are observed in early stages of development and putative silencers, the functional significance of cis-regulatory elements lacking H3K27ac is poorly understood. Here we show that macroH2A histone variants mark a subset of enhancers in normal and cancer cells, which we coined 'macro-Bound Enhancers', that modulate enhancer activity. We find macroH2A variants localized at enhancer elements that are devoid of H3K27ac in a cell type-specific manner, indicating a role for macroH2A at inactive enhancers to maintain cell identity. In following, reactivation of macro-bound enhancers is associated with oncogenic programs in breast cancer and their repressive role is correlated with the activity of macroH2A2 as a negative regulator of BRD4 chromatin occupancy. Finally, through single cell epigenomic profiling of normal mammary stem cells derived from mice, we show that macroH2A deficiency facilitates increased activity of transcription factors associated with stem cell activity.
    DOI:  https://doi.org/10.1038/s42003-023-04571-1
  6. Elife. 2023 Feb 20. pii: e80840. [Epub ahead of print]12
    eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways.
    OCCAMS Consortium
      Cancer is driven by both genetic and epigenetic changes that impact on gene expression profiles and the resulting tumourigenic phenotype. Enhancers are transcriptional regulatory elements that are key to our understanding of how this rewiring of gene expression is achieved in cancer cells. Here we have harnessed the power of RNA-seq data from hundreds of patients with oesophageal adenocarcinoma (OAC) or its precursor state Barrett's oesophagus (BO) coupled with open chromatin maps to identify potential enhancer RNAs (eRNAs) and their associated enhancer regions in this cancer. We identify ~1000 OAC-specific enhancers and use this data to uncover new cellular pathways that are operational in OAC. Among these are enhancers for JUP, MYBL2 and CCNE1, and we show that their activity is required for cancer cell viability. We also demonstrate the clinical utility of our dataset for identifying disease stage and patient prognosis. Our data therefore identify an important set of regulatory elements that enhance our molecular understanding of OAC and point to potential new therapeutic directions.
    Keywords:  cancer biology; chromosomes; gene expression; human
    DOI:  https://doi.org/10.7554/eLife.80840
  7. Methods Mol Biol. 2023 ;2611 155-185
    Single-Cell Joint Profiling of Open Chromatin and Transcriptome by Paired-Seq.
    Chenxu Zhu, Zhaoning Wang, Bing Ren.
      Simultaneous detection of chromatin accessibility and transcription from the same cells promises to greatly facilitate the dissection of cell-type-specific gene regulatory programs in complex tissues. Paired-seq enables joint analysis of open chromatin and nuclear transcriptome from up to a million cells in parallel. It achieves ultra-high-throughput single-cell multiomics with the use of a combinatorial barcoding strategy involving sequential ligation of multiplexed DNA barcodes to chromatin DNA fragments and reverse transcription products, followed by high-throughput DNA sequencing of the resulting DNA libraries and deconvolution of single-cell multiomic maps based on cell-specific barcodes.
    Keywords:  Chromatin accessibility; Epigenome; Gene expression; Paired-seq; Single-cell multiomics
    DOI:  https://doi.org/10.1007/978-1-0716-2899-7_10
  8. Methods Mol Biol. 2023 ;2611 231-247
    Simultaneous Measurement of DNA Methylation and Nucleosome Occupancy in Single Cells Using scNOMe-Seq.
    Michael Wasney, Sebastian Pott.
      Single-cell Nucleosome Occupancy and Methylome sequencing (scNOMe-seq) is a multimodal assay that simultaneously measures endogenous DNA methylation and nucleosome occupancy (i.e., chromatin accessibility) in single cells. scNOMe-seq combines the activity of a GpC Methyltransferase, an enzyme which methylates cytosines in GpC dinucleotides, with bisulfite conversion, whereby unmethylated cytosines are converted into thymines. Because GpC Methyltransferase acts only on cytosines present in non-nucleosomal regions of the genome, the subsequent bisulfite conversion step not only detects the endogenous DNA methylation, but also reveals the genome-wide pattern of chromatin accessibility. Implementing this technology at the single-cell level helps to capture the dynamics governing methylation and accessibility vary across individual cells and cell types. Here, we provide a scalable plate-based protocol for preparing scNOMe-seq libraries from single nucleus suspensions.
    Keywords:  Bisulfite sequencing; Chromatin accessibility; DNA methylation; Epigenetic modification; Fluorescence-activated cell sorting; GpC Methyltransferase; Nucleosome occupancy; Single cell; scNOMe-seq
    DOI:  https://doi.org/10.1007/978-1-0716-2899-7_12
  9. Nucleic Acids Res. 2023 Feb 20. pii: gkad072. [Epub ahead of print]
    PBRM1 bromodomains associate with RNA to facilitate chromatin association.
    Saumya M De Silva, Alisha Dhiman, Surbhi Sood, Kilsia F Mercedes, William J Simmons, Morkos A Henen, Beat Vögeli, Emily C Dykhuizen, Catherine A Musselman.
      PBRM1 is a subunit of the PBAF chromatin remodeling complex, which is mutated in 40-50% of clear cell renal cell carcinoma patients. It is thought to largely function as a chromatin binding subunit of the PBAF complex, but the molecular mechanism underlying this activity is not fully known. PBRM1 contains six tandem bromodomains which are known to cooperate in binding of nucleosomes acetylated at histone H3 lysine 14 (H3K14ac). Here, we demonstrate that the second and fourth bromodomains from PBRM1 also bind nucleic acids, selectively associating with double stranded RNA elements. Disruption of the RNA binding pocket is found to compromise PBRM1 chromatin binding and inhibit PBRM1-mediated cellular growth effects.
    DOI:  https://doi.org/10.1093/nar/gkad072
  10. Genome Res. 2023 Feb 21. pii: gr.277559.122. [Epub ahead of print]
    Kinetic networks identify TWIST2 as a key regulatory node in adipogenesis.
    Arun B Dutta, Daniel S Lank, Roza K Przanowska, Piotr Przanowski, Lixin Wang, Bao Nguyen, Ninad M Walavalkar, Fabiana M Duarte, Michael J Guertin.
      Adipocytes contribute to metabolic disorders such as obesity, diabetes, and atherosclerosis. Prior characterizations of the transcriptional network driving adipogenesis overlook transiently acting transcription factors (TFs), genes, and regulatory elements that are essential for proper differentiation. Moreover, traditional gene regulatory networks provide neither mechanistic details about individual RE-gene relationships nor temporal information needed to define a regulatory hierarchy that prioritizes key regulatory factors. To address these shortcomings, we integrate kinetic chromatin accessibility (ATAC-seq) and nascent transcription (PRO-seq) data to generate temporally resolved networks that describe TF binding events and resultant effects on target gene expression. Our data indicate which TF families cooperate with and antagonize each other to regulate adipogenesis. Compartment modeling of RNA polymerase density quantifies how individual TFs mechanistically contribute to distinct steps in transcription. Glucocorticoid receptor activates transcription by inducing RNA polymerase pause release while SP and AP-1 factors affect RNA polymerase initiation. We identify Twist2 as a previously unappreciated effector of adipocyte differentiation. We find that TWIST2 acts as a negative regulator of 3T3-L1 and primary preadipocyte differentiation. We confirm that Twist2 knockout mice have compromised lipid storage within subcutaneous and brown adipose tissue. Previous phenotyping of Twist2 knockout mice and Setleis syndrome Twist2 -/- patients noted deficiencies in subcutaneous adipose tissue. This network inference framework is a powerful and general approach for interpreting complex biological phenomena and can be applied to a wide range of cellular processes.
    DOI:  https://doi.org/10.1101/gr.277559.122
  11. Cell Death Differ. 2023 Feb 24.
    BAP18 facilitates CTCF-mediated chromatin accessible to regulate enhancer activity in breast cancer.
    Ge Sun, Yuntao Wei, Baosheng Zhou, Manlin Wang, Ruina Luan, Yu Bai, Hao Li, Shan Wang, Dantong Zheng, Chunyu Wang, Shengli Wang, Kai Zeng, Shuchang Liu, Lin Lin, Mingcong He, Qiang Zhang, Yue Zhao.
      The estrogen receptor alpha (ERα) signaling pathway is a crucial target for ERα-positive breast cancer therapeutic strategies. Co-regulators and other transcription factors cooperate for effective ERα-related enhancer activation. Recent studies demonstrate that the transcription factor CTCF is essential to participate in ERα/E2-induced enhancer transactivation. However, the mechanism of how CTCF is achieved remains unknown. Here, we provided evidence that BAP18 is required for CTCF recruitment on ERα-enriched enhancers, facilitating CTCF-mediated chromatin accessibility to promote enhancer RNAs transcription. Consistently, GRO-seq demonstrates that the enhancer activity is positively correlated with BAP18 enrichment. Furthermore, BAP18 interacts with SMARCA1/BPTF to accelerate the recruitment of CTCF to ERα-related enhancers. Interestingly, BAP18 is involved in chromatin accessibility within enhancer regions, thereby increasing enhancer transactivation and enhancer-promoter looping. BAP18 depletion increases the sensitivity of anti-estrogen and anti-enhancer treatment in MCF7 cells. Collectively, our study indicates that BAP18 coordinates with CTCF to enlarge the transactivation of ERα-related enhancers, providing a better understanding of BAP18/CTCF coupling chromatin remodeling and E-P looping in the regulation of enhancer transcription.
    DOI:  https://doi.org/10.1038/s41418-023-01135-y
  12. Nat Commun. 2023 Feb 17. 14(1): 913
    Widespread perturbation of ETS factor binding sites in cancer.
    Sebastian Carrasco Pro, Heather Hook, David Bray, Daniel Berenzy, Devlin Moyer, Meimei Yin, Adam Thomas Labadorf, Ryan Tewhey, Trevor Siggers, Juan Ignacio Fuxman Bass.
      Although >90% of somatic mutations reside in non-coding regions, few have been reported as cancer drivers. To predict driver non-coding variants (NCVs), we present a transcription factor (TF)-aware burden test based on a model of coherent TF function in promoters. We apply this test to NCVs from the Pan-Cancer Analysis of Whole Genomes cohort and predict 2555 driver NCVs in the promoters of 813 genes across 20 cancer types. These genes are enriched in cancer-related gene ontologies, essential genes, and genes associated with cancer prognosis. We find that 765 candidate driver NCVs alter transcriptional activity, 510 lead to differential binding of TF-cofactor regulatory complexes, and that they primarily impact the binding of ETS factors. Finally, we show that different NCVs within a promoter often affect transcriptional activity through shared mechanisms. Our integrated computational and experimental approach shows that cancer NCVs are widespread and that ETS factors are commonly disrupted.
    DOI:  https://doi.org/10.1038/s41467-023-36535-8
  13. Neuron. 2023 Feb 17. pii: S0896-6273(23)00072-7. [Epub ahead of print]
    DNA-initiated epigenetic cascades driven by C9orf72 hexanucleotide repeat.
    Yang Liu, Zhiyuan Huang, Honghe Liu, Zhicheng Ji, Amit Arora, Danfeng Cai, Hongjin Wang, Mingming Liu, Eric A J Simko, Yanjun Zhang, Goran Periz, Zhe Liu, Jiou Wang.
      The C9orf72 hexanucleotide repeat expansion (HRE) is the most frequent genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we describe the pathogenic cascades that are initiated by the C9orf72 HRE DNA. The HRE DNA binds to its protein partner DAXX and promotes its liquid-liquid phase separation, which is capable of reorganizing genomic structures. An HRE-dependent nuclear accumulation of DAXX drives chromatin remodeling and epigenetic changes such as histone hypermethylation and hypoacetylation in patient cells. While regulating global gene expression, DAXX plays a key role in the suppression of basal and stress-inducible expression of C9orf72 via chromatin remodeling and epigenetic modifications of the promoter of the major C9orf72 transcript. Downregulation of DAXX or rebalancing the epigenetic modifications mitigates the stress-induced sensitivity of C9orf72-patient-derived motor neurons. These studies reveal a C9orf72 HRE DNA-dependent regulatory mechanism for both local and genomic architectural changes in the relevant diseases.
    Keywords:  ALS; C9orf72; DAXX; DNA; FTD; chromatin; epigenetic; neurodegeneration; phase separation; transcription
    DOI:  https://doi.org/10.1016/j.neuron.2023.01.022
  14. Nat Biotechnol. 2023 Feb 23.
    Retrospective analysis of enhancer activity and transcriptome history.
    Ruben Boers, Joachim Boers, Beatrice Tan, Marieke E van Leeuwen, Evelyne Wassenaar, Erlantz Gonzalez Sanchez, Esther Sleddens, Yasha Tenhagen, Eskeatnaf Mulugeta, Joop Laven, Menno Creyghton, Willy Baarends, Wilfred F J van IJcken, Joost Gribnau.
      Cell state changes in development and disease are controlled by gene regulatory networks, the dynamics of which are difficult to track in real time. In this study, we used an inducible DCM-RNA polymerase subunit b fusion protein which labels active genes and enhancers with a bacterial methylation mark that does not affect gene transcription and is propagated in S-phase. This DCM-RNA polymerase fusion protein enables transcribed genes and active enhancers to be tagged and then examined at later stages of development or differentiation. We apply this DCM-time machine (DCM-TM) technology to study intestinal homeostasis, revealing rapid and coordinated activation of enhancers and nearby genes during enterocyte differentiation. We provide new insights in absorptive-secretory lineage decision-making in intestinal stem cell (ISC) differentiation and show that ISCs retain a unique chromatin landscape required to maintain ISC identity and delineate future expression of differentiation-associated genes. DCM-TM has wide applicability in tracking cell states, providing new insights in the regulatory networks underlying cell state changes.
    DOI:  https://doi.org/10.1038/s41587-023-01683-1
  15. Nucleic Acids Res. 2023 Feb 20. pii: gkad058. [Epub ahead of print]
    Comprehensive chromatin proteomics resolves functional phases of pluripotency and identifies changes in regulatory components.
    Enes Ugur, Alexandra de la Porte, Weihua Qin, Sebastian Bultmann, Alina Ivanova, Micha Drukker, Matthias Mann, Michael Wierer, Heinrich Leonhardt.
      The establishment of cellular identity is driven by transcriptional and epigenetic regulators of the chromatin proteome - the chromatome. Comprehensive analyses of the chromatome composition and dynamics can therefore greatly improve our understanding of gene regulatory mechanisms. Here, we developed an accurate mass spectrometry (MS)-based proteomic method called Chromatin Aggregation Capture (ChAC) followed by Data-Independent Acquisition (DIA) and analyzed chromatome reorganizations during major phases of pluripotency. This enabled us to generate a comprehensive atlas of proteomes, chromatomes, and chromatin affinities for the ground, formative and primed pluripotency states, and to pinpoint the specific binding and rearrangement of regulatory components. These comprehensive datasets combined with extensive analyses identified phase-specific factors like QSER1 and JADE1/2/3 and provide a detailed foundation for an in-depth understanding of mechanisms that govern the phased progression of pluripotency. The technical advances reported here can be readily applied to other models in development and disease.
    DOI:  https://doi.org/10.1093/nar/gkad058
  16. Plant Cell. 2023 Feb 23. pii: koad054. [Epub ahead of print]
    Enhancer activation via TCP and HD-ZIP and repression by Dof transcription factors mediate giant cell-specific expression.
    Lilan Hong, Byron Rusnak, Clint S Ko, Shouling Xu, Xi He, Dengying Qiu, S Earl Kang, Jose L Pruneda-Paz, Adrienne H K Roeder.
      Proper cell-type identity relies on highly coordinated regulation of gene expression. Regulatory elements such as enhancers can produce cell type-specific expression patterns, but the mechanisms underlying specificity are not well understood. We previously identified an enhancer region capable of driving specific expression in giant cells, which are large, highly endoreduplicated cells in the Arabidopsis thaliana sepal epidermis. In this study, we use the giant cell enhancer as a model to understand the regulatory logic that promotes cell type-specific expression. Our dissection of the enhancer revealed that giant cell specificity is mediated primarily through the combination of two activators and one repressor. HD-ZIP and TCP transcription factors are involved in the activation of expression throughout the epidermis. High expression of HD-ZIP transcription factor genes in giant cells promoted higher expression driven by the enhancer in giant cells. Dof transcription factors repressed the activity of the enhancer such that only giant cells have higher expression levels driven by the enhancer. Thus, our data are consistent with a conceptual model whereby cell type-specific expression emerges from the combined activities of three transcription factor families activating and repressing expression in epidermal cells.
    Keywords:  Arabidopsis; Dof; HD-ZIP; TCP; endoreduplication; enhancer; flower development; giant cell; sepal
    DOI:  https://doi.org/10.1093/plcell/koad054
  17. Cell Rep. 2023 Feb 23. pii: S2211-1247(23)00174-2. [Epub ahead of print]42(3): 112163
    JMJ28 guides sequence-specific targeting of ATX1/2-containing COMPASS-like complex in Arabidopsis.
    Si-Si Xie, Yi-Zhe Zhang, Li Peng, Ding-Tian Yu, Guohui Zhu, Qingzhen Zhao, Chun-Han Wang, Qi Xie, Cheng-Guo Duan.
      Despite extensive investigations in mammals and yeasts, the importance and specificity of COMPASS-like complex, which catalyzes histone 3 lysine 4 methylation (H3K4me), are not fully understood in plants. Here, we report that JMJ28, a Jumonji C domain-containing protein in Arabidopsis, recognizes specific DNA motifs through a plant-specific WRC domain and acts as an interacting factor to guide the chromatin targeting of ATX1/2-containing COMPASS-like complex. JMJ28 associates with COMPASS-like complex in vivo via direct interaction with RBL. The DNA-binding activity of JMJ28 is essential for both the targeting specificity of ATX1/2-COMPASS and the deposition of H3K4me at specific loci but exhibit functional redundancy with alternative COMPASS-like complexes at other loci. Finally, we demonstrate that JMJ28 is a negative regulator of plant immunity. In summary, our findings reveal a plant-specific recruitment mechanism of COMPASS-like complex. These findings help to gain deeper insights into the regulatory mechanism of COMPASS-like complex in plants.
    Keywords:  ATX1; ATX2; COMPASS complex; CP: Plants; DNA binding; H3K4 methylation; JMJ28; RBL; epigenetics; histone demethylase; plant immunity
    DOI:  https://doi.org/10.1016/j.celrep.2023.112163
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