STAG2 Mutations Alter CTCF-Anchored Loop Extrusion, Reduce Cis-Regulatory Interactions and EWSR1-FLI1 Activity in Ewing Sarcoma

Using isogenic Ewing cells, researchers showed STAG2 loss of function profoundly changed the transcriptome but it did not significantly impact EWSR1-FLI1, CTCF/cohesin, or acetylated H3K27 DNA binding patterns.
[Cancer Cell]
Surdez, D., Zaidi, S., Grossetête, S., Laud-Duval, K., Ferre, A. S., Mous, L., Vourc’h, T., Tirode, F., Pierron, G., Raynal, V., Baulande, S., Brunet, E., Hill, V., & Delattre, O. (2021). STAG2 mutations alter CTCF-anchored loop extrusion, reduce cis-regulatory interactions and EWSR1-FLI1 activity in Ewing sarcoma. Cancer Cell, 0(0). https://doi.org/10.1016/j.ccell.2021.04.001 Cite
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A Selective HDAC8 Inhibitor Potentiates Antitumor Immunity and Efficacy of Immune Checkpoint Blockade in Hepatocellular Carcinoma

The authors demonstrated that selective HDAC8 inhibition elicited effective and durable responses to immune-checkpoint blockade by co-opting adaptive immunity through enhancer reprogramming.
[Science Translational Medicine]
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Depletion of H3K36me2 Recapitulates Epigenomic and Phenotypic Changes Induced by the H3.3K36M Oncohistone Mutation

Researchers specifically depleted H3K36me2 or H3K36me3 in mesenchymal cells, using CRISPR-Cas9 to separately knock out the corresponding methyltransferases NSD1/2 or SETD2.
[Proceedings of the National Academy of Sciences of the United States of America]

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MED19 Alters AR Occupancy and Gene Expression in Prostate Cancer Cells, Driving MAOA Expression and Growth under Low Androgen

Scientists showed that stable overexpression of MED19 in androgen-dependent LNCaP cells promoted growth under conditions of androgen deprivation.
[PLoS Genetics]
Weber, H., Ruoff, R., & Garabedian, M. J. (2021). MED19 alters AR occupancy and gene expression in prostate cancer cells, driving MAOA expression and growth under low androgen. PLOS Genetics, 17(1), e1008540. https://doi.org/10.1371/journal.pgen.1008540 Cite
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The Epigenetic Regulator Mll1 Is Required for Wnt-Driven Intestinal Tumorigenesis and Cancer Stemness

Investigators identified the histone methyltransferase Mll1 as a regulator of Wnt-driven intestinal cancer. Mll1 is highly expressed in Lgr5+ stem cells and human colon carcinomas with increased nuclear β-catenin.
[Nature Communications]
Grinat, J., Heuberger, J., Vidal, R. O., Goveas, N., Kosel, F., Berenguer-Llergo, A., Kranz, A., Wulf-Goldenberg, A., Behrens, D., Melcher, B., Sauer, S., Vieth, M., Batlle, E., Stewart, A. F., & Birchmeier, W. (2020). The epigenetic regulator Mll1 is required for Wnt-driven intestinal tumorigenesis and cancer stemness. Nature Communications, 11(1), 6422. https://doi.org/10.1038/s41467-020-20222-z Cite
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Comprehensive Landscape of Epigenetic-Dysregulated lncRNAs Reveals a Profound Role of Enhancers in Carcinogenesis in Breast Cancer Subtypes

The authors analyzed the epigenetic alterations of long non-coding RNAs (lncRNAs) at important regulatory elements in three breast cancer subtypes.
[Molecular Therapy-Nucleic Acids]
Comprehensive landscape of epigenetic-dysregulated lncRNAs reveals a profound role of enhancers in carcinogenesis in breast cancer subtypes: Molecular Therapy - Nucleic Acids. (n.d.). Retrieved January 5, 2021, from https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(20)30405-4 Cite
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H1 Histones Control the Epigenetic Landscape by Local Chromatin Compaction

Researchers generated a conditional triple-H1-knockout mouse strain and depleted H1 in haematopoietic cells. H1 depletion in T cells leads to de-repression of T cell activation genes, a process that mimics normal T cell activation.
[Nature]
Willcockson, M. A., Healton, S. E., Weiss, C. N., Bartholdy, B. A., Botbol, Y., Mishra, L. N., Sidhwani, D. S., Wilson, T. J., Pinto, H. B., Maron, M. I., Skalina, K. A., Toro, L. N., Zhao, J., Lee, C.-H., Hou, H., Yusufova, N., Meydan, C., Osunsade, A., David, Y., … Skoultchi, A. I. (2020). H1 histones control the epigenetic landscape by local chromatin compaction. Nature, 1–6. https://doi.org/10.1038/s41586-020-3032-z Cite
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Endothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis through CCL2-Mediated Angiocrine Signaling

In vitro, epigenome‐editing of carbon tetrachloride (CCL2) enhancer and promoter regions by CRISPR‐dCas9‐KRAB technology repressed TNFα‐induced CCL2 transcription via H3K9 tri‐methylation.
[Hepatology]
Gao, J., Wei, B., Liu, M., Hirsova, P., Sehrawat, T. S., Cao, S., Hu, X., Xue, F., Yaqoob, U., Kang, N., Cui, H., Pomerantz, W. C. K., Kostallari, E., & Shah, V. H. (n.d.). Endothelial p300 promotes portal hypertension and hepatic fibrosis through CCL2-mediated angiocrine signaling. Hepatology, n/a(n/a). https://doi.org/https://doi.org/10.1002/hep.31617 Cite
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Transcriptional Profile of Platelets and iPSC-Derived Megakaryocytes from Whole Genome and RNA Sequencing

In 290 normal subjects from the GeneSTAR Research Study, investigators generated whole genome sequence data from whole blood and RNA sequence data from extracted non-ribosomal RNA from 185 induced pluripotent stem cell-derived megakaryocyte cell lines and 290 blood platelet samples from these subjects.
[Blood]
Kammers, K., Taub, M., Rodriguez, B., Yanek, L. R., Ruczinski, I., Martin, J., Kanchan, K., Battle, A., Cheng, L., Wang, Z. Z., Johnson, A. D., Leek, J., Faraday, N., Becker, L., & Mathias, R. (n.d.). Transcriptional profile of platelets and iPSC-derived megakaryocytes from whole genome and RNA sequencing. Blood. https://doi.org/10.1182/blood.2020006115 Cite
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Identification of a Distal Locus Enhancer Element That Controls Cell Type–Specific TNF and LTA Gene Expression in Human T Cells

Scientists showed that a highly conserved NFAT binding site within the distal noncoding element hHS-8 coordinately controlled TNF and LTA gene expression in human T cells.
[Journal of Immunology]
Jasenosky, L. D., Nambu, A., Tsytsykova, A. V., Ranjbar, S., Haridas, V., Kruidenier, L., Tough, D. F., & Goldfeld, A. E. (2020). Identification of a Distal Locus Enhancer Element That Controls Cell Type–Specific TNF and LTA Gene Expression in Human T Cells. The Journal of Immunology, 205(9), 2479–2488. https://doi.org/10.4049/jimmunol.1901311 Cite
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LncRNA HotairM1 Depletion Promotes Self-Renewal of Cancer Stem Cells Through HOXA1-Nanog Regulation Loop

Based on analysis of transcriptome sequencing, researchers identified a long noncoding RNA (lncRNA) named HotairM1 that was weakly expressed in human colorectal carcinoma and uveal melanoma, and a much lower expression in corresponding CSCs.
[Molecular Therapy-Nucleic Acids]
Li, F., Xu, Y., Xu, X., Ge, S., Zhang, F., Zhang, H., & Fan, X. (2020). LncRNA HotairM1 Depletion Promotes Self-Renewal of Cancer Stem Cells through HOXA1-Nanog regulation loop. Molecular Therapy - Nucleic Acids, 0(0). https://doi.org/10.1016/j.omtn.2020.09.008 Cite
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