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31 results on '"Crump, Nicholas T."'

1. Disrupted propionate metabolism evokes transcriptional changes in the heart by increasing histone acetylation and propionylation

Author

Park, Kyung Chan, Crump, Nicholas T., Louwman, Niamh, Krywawych, Steve, Cheong, Yuen Jian, Vendrell, Iolanda, Gill, Eleanor K., Gunadasa-Rohling, Mala, Ford, Kerrie L., Hauton, David, Fournier, Marjorie, Pires, Elisabete, Watson, Lydia, Roseman, Gerald, Holder, James, Koschinski, Andreas, Carnicer, Ricardo, Curtis, M. Kate, Zaccolo, Manuela, Hulikova, Alzbeta, Fischer, Roman, Kramer, Holger B., McCullagh, James S. O., Trefely, Sophie, Milne, Thomas A., and Swietach, Pawel

Published
2023
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3. MLL-AF4 cooperates with PAF1 and FACT to drive high-density enhancer interactions in leukemia

Author

Crump, Nicholas T., Smith, Alastair L., Godfrey, Laura, Dopico-Fernandez, Ana M., Denny, Nicholas, Harman, Joe R., Hamley, Joseph C., Jackson, Nicole E., Chahrour, Catherine, Riva, Simone, Rice, Siobhan, Kim, Jaehoon, Basrur, Venkatesha, Fermin, Damian, Elenitoba-Johnson, Kojo, Roeder, Robert G., Allis, C. David, Roberts, Irene, Roy, Anindita, Geng, Huimin, Davies, James O. J., and Milne, Thomas A.

Published
2023
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4. H3K79me2/3 controls enhancer–promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells

Author

Godfrey, Laura, Crump, Nicholas T, O’Byrne, Sorcha, Lau, I-Jun, Rice, Siobhan, Harman, Joe R, Jackson, Thomas, Elliott, Natalina, Buck, Gemma, Connor, Christopher, Thorne, Ross, Knapp, David JHF, Heidenreich, Olaf, Vyas, Paresh, Menendez, Pablo, Inglott, Sarah, Ancliff, Philip, Geng, Huimin, Roberts, Irene, Roy, Anindita, and Milne, Thomas A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Oncology and Carcinogenesis, Orphan Drug, Hematology, Pediatric Cancer, Stem Cell Research - Nonembryonic - Non-Human, Rare Diseases, Stem Cell Research, Cancer, Pediatric, Genetics, Aetiology, 2.1 Biological and endogenous factors, AC133 Antigen, Biomarkers, Tumor, Cell Line, Tumor, Cell Transformation, Neoplastic, Enhancer Elements, Genetic, Gene Expression Regulation, Leukemic, Gene Silencing, Histones, Humans, Immunophenotyping, Leukemia, Models, Biological, Myeloid-Lymphoid Leukemia Protein, Neoplastic Stem Cells, Oncogene Proteins, Fusion, Promoter Regions, Genetic, Protein Binding, Immunology, Cardiovascular medicine and haematology, Clinical sciences, Oncology and carcinogenesis
Abstract

MLL gene rearrangements (MLLr) are a common cause of aggressive, incurable acute lymphoblastic leukemias (ALL) in infants and children, most of which originate in utero. The most common MLLr produces an MLL-AF4 fusion protein. MLL-AF4 promotes leukemogenesis by activating key target genes, mainly through recruitment of DOT1L and increased histone H3 lysine-79 methylation (H3K79me2/3). One key MLL-AF4 target gene is PROM1, which encodes CD133 (Prominin-1). CD133 is a pentaspan transmembrane glycoprotein that represents a potential pan-cancer target as it is found on multiple cancer stem cells. Here we demonstrate that aberrant PROM1/CD133 expression is essential for leukemic cell growth, mediated by direct binding of MLL-AF4. Activation is controlled by an intragenic H3K79me2/3 enhancer element (KEE) leading to increased enhancer-promoter interactions between PROM1 and the nearby gene TAPT1. This dual locus regulation is reflected in a strong correlation of expression in leukemia. We find that in PROM1/CD133 non-expressing cells, the PROM1 locus is repressed by polycomb repressive complex 2 (PRC2) binding, associated with reduced expression of TAPT1, partially due to loss of interactions with the PROM1 locus. Together, these results provide the first detailed analysis of PROM1/CD133 regulation that explains CD133 expression in MLLr ALL.

Published
2021

5. Potent, p53-independent induction of NOXA sensitizes MLL-rearranged B-cell acute lymphoblastic leukemia cells to venetoclax

Author

Fidyt, Klaudyna, Pastorczak, Agata, Cyran, Julia, Crump, Nicholas T., Goral, Agnieszka, Madzio, Joanna, Muchowicz, Angelika, Poprzeczko, Martyna, Domka, Krzysztof, Komorowski, Lukasz, Winiarska, Magdalena, Harman, Joe R., Siudakowska, Karolina, Graczyk-Jarzynka, Agnieszka, Patkowska, Elzbieta, Lech-Maranda, Ewa, Mlynarski, Wojciech, Golab, Jakub, Milne, Thomas A., and Firczuk, Malgorzata

Published
2022
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7. A human fetal liver-derived infant MLL-AF4 acute lymphoblastic leukemia model reveals a distinct fetal gene expression program

Author

Rice, Siobhan, Jackson, Thomas, Crump, Nicholas T., Fordham, Nicholas, Elliott, Natalina, O’Byrne, Sorcha, Fanego, Maria del Mar Lara, Addy, Dilys, Crabb, Trisevgeni, Dryden, Carryl, Inglott, Sarah, Ladon, Dariusz, Wright, Gary, Bartram, Jack, Ancliff, Philip, Mead, Adam J., Halsey, Christina, Roberts, Irene, Milne, Thomas A., and Roy, Anindita

Published
2021
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9. Discovery of a CD10-negative B-progenitor in human fetal life identifies unique ontogeny-related developmental programs

Author

O'Byrne, Sorcha, Elliott, Natalina, Rice, Siobhan, Buck, Gemma, Fordham, Nicholas, Garnett, Catherine, Godfrey, Laura, Crump, Nicholas T., Wright, Gary, Inglott, Sarah, Hua, Peng, Psaila, Bethan, Povinelli, Benjamin, Knapp, David J.H.F., Agraz-Doblas, Antonio, Bueno, Clara, Varela, Ignacio, Bennett, Phillip, Koohy, Hashem, Watt, Suzanne M., Karadimitris, Anastasios, Mead, Adam J., Ancliff, Phillip, Vyas, Paresh, Menendez, Pablo, Milne, Thomas A., Roberts, Irene, and Roy, Anindita

Published
2019
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13. Establishment and Characterization of a Model of Acquired Resistance to DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic Leukemia Cells

Author

Schneider, Pauline, primary, Arentsen-Peters, Susan T.C.J.M., additional, Crump, Nicholas T., additional, Smith, Alastair, additional, Hagelaar, Rico, additional, Adriaanse, Fabienne R.S., additional, Bos, Romy S., additional, Vrenken, Kirsten S., additional, rockx-Brouwer, Dedeke, additional, Tang, Ziqin, additional, Vermeij, Wilbert P., additional, De Jong, Anja, additional, Koopmans, Bianca, additional, Dolman, M.Emmy M., additional, Milne, Thomas A., additional, Pieters, Rob, additional, and Stam, Ronald W., additional

Published
2022
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15. PAF1 and FACT cooperate with MLL-AF4 to drive enhancer activity in leukemia

Author

Crump, Nicholas T., primary, Smith, Alastair, additional, Godfrey, Laura, additional, Jackson, Nicole, additional, Rice, Siobhan, additional, Kim, Jaehoon, additional, Basrur, Venkatesha, additional, Fermin, Damian, additional, Elenitoba-Johnson, Kojo, additional, Roeder, Robert G., additional, Allis, C. David, additional, Roberts, Irene, additional, Roy, Anindita, additional, and Milne, Thomas, additional

Published
2022
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17. A KMT2A-AFF1 gene regulatory network highlights the role of core transcription factors and reveals the regulatory logic of key downstream target genes

Author

Harman, Joe R., primary, Thorne, Ross, additional, Jamilly, Max, additional, Tapia, Marta, additional, Crump, Nicholas T., additional, Rice, Siobhan, additional, Beveridge, Ryan, additional, Morrissey, Edward, additional, de Bruijn, Marella F.T.R., additional, Roberts, Irene, additional, Roy, Anindita, additional, Fulga, Tudor A., additional, and Milne, Thomas A., additional

Published
2021
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18. Chromatin accessibility governs the differential response of cancer and T cells to arginine starvation

Author

Crump, Nicholas T., primary, Hadjinicolaou, Andreas V., additional, Xia, Meng, additional, Walsby-Tickle, John, additional, Gileadi, Uzi, additional, Chen, Ji-Li, additional, Setshedi, Mashiko, additional, Olsen, Lars R., additional, Lau, I-Jun, additional, Godfrey, Laura, additional, Quek, Lynn, additional, Yu, Zhanru, additional, Ballabio, Erica, additional, Barnkob, Mike B., additional, Napolitani, Giorgio, additional, Salio, Mariolina, additional, Koohy, Hashem, additional, Kessler, Benedikt M., additional, Taylor, Stephen, additional, Vyas, Paresh, additional, McCullagh, James S.O., additional, Milne, Thomas A., additional, and Cerundolo, Vincenzo, additional

Published
2021
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19. A novel human fetal liver-derived model reveals that MLL-AF4 drives a distinct fetal gene expression program in infant ALL

Author

Rice, Siobhan, primary, Jackson, Thomas, additional, Crump, Nicholas T, additional, Fordham, Nicholas, additional, Elliott, Natalina, additional, O’Byrne, Sorcha, additional, Inglott, Sarah, additional, Ladon, Dariusz, additional, Wright, Gary, additional, Bartram, Jack, additional, Ancliff, Philip, additional, Mead, Adam J, additional, Halsey, Christina, additional, Roberts, Irene, additional, Milne, Thomas A, additional, and Roy, Anindita, additional

Published
2020
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20. Pharmacological Induction of NOXA Sensitizes High-Risk B Cell Acute Lymphoblastic Leukemia Cells to Venetoclax

Author

Fidyt, Klaudyna, primary, Cyran, Julia, additional, Pastorczak, Agata, additional, Crump, Nicholas T., additional, Muchowicz, Angelika, additional, Goral, Agnieszka, additional, Domka, Krzysztof, additional, Komorowski, Lukasz, additional, Siudakowska, Karolina, additional, Graczyk-Jarzynka, Agnieszka, additional, Patkowska, Elzbieta, additional, Winiarska, Magdalena, additional, Golab, Jakub, additional, Milne, Thomas A., additional, and Firczuk, Malgorzata, additional

Published
2020
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21. Phenotypic analysis of an MLL-AF4 gene regulatory network reveals indirect CASP9 repression as a mode of inducing apoptosis resistance

Author

Harman, Joe R., primary, Thorne, Ross, additional, Jamilly, Max, additional, Tapia, Marta, additional, Crump, Nicholas T., additional, Rice, Siobhan, additional, Beveridge, Ryan, additional, Morrissey, Edward, additional, de Bruijn, Marella F.T.R, additional, Roberts, Irene, additional, Roy, Anindita, additional, Fulga, Tudor A., additional, and Milne, Thomas A., additional

Published
2020
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22. H3K79me2/3 controls enhancer–promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells

Author

Godfrey, Laura, primary, Crump, Nicholas T., additional, O’Byrne, Sorcha, additional, Lau, I-Jun, additional, Rice, Siobhan, additional, Harman, Joe R., additional, Jackson, Thomas, additional, Elliott, Natalina, additional, Buck, Gemma, additional, Connor, Christopher, additional, Thorne, Ross, additional, Knapp, David J. H. F., additional, Heidenreich, Olaf, additional, Vyas, Paresh, additional, Menendez, Pablo, additional, Inglott, Sarah, additional, Ancliff, Philip, additional, Geng, Huimin, additional, Roberts, Irene, additional, Roy, Anindita, additional, and Milne, Thomas A., additional

Published
2020
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24. Discovery of a CD10-negative B-progenitor in human fetal life identifies unique ontogeny-related developmental programs

Author

O’Byrne, Sorcha, primary, Elliott, Natalina, additional, Rice, Siobhan, additional, Buck, Gemma, additional, Fordham, Nicholas, additional, Garnett, Catherine, additional, Godfrey, Laura, additional, Crump, Nicholas T., additional, Wright, Gary, additional, Inglott, Sarah, additional, Hua, Peng, additional, Psaila, Bethan, additional, Povinelli, Benjamin, additional, Knapp, David J. H. F., additional, Agraz-Doblas, Antonio, additional, Bueno, Clara, additional, Varela, Ignacio, additional, Bennett, Phillip, additional, Koohy, Hashem, additional, Watt, Suzanne M., additional, Karadimitris, Anastasios, additional, Mead, Adam J., additional, Ancliff, Phillip, additional, Vyas, Paresh, additional, Menendez, Pablo, additional, Milne, Thomas A., additional, Roberts, Irene, additional, and Roy, Anindita, additional

Published
2019
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27. Cover Picture: Live‐Cell Studies of p300/CBP Histone Acetyltransferase Activity and Inhibition (ChemBioChem 14/2012)

Author

Dancy, Beverley M., primary, Crump, Nicholas T., additional, Peterson, Daniel J., additional, Mukherjee, Chandrani, additional, Bowers, Erin M., additional, Ahn, Young‐Hoon, additional, Yoshida, Minoru, additional, Zhang, Jin, additional, Mahadevan, Louis C., additional, Meyers, David J., additional, Boeke, Jef D., additional, and Cole, Philip A., additional

Published
2012
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28. Live-Cell Studies of p300/CBP Histone Acetyltransferase Activity and Inhibition

Author

Dancy, Beverley M., primary, Crump, Nicholas T., additional, Peterson, Daniel J., additional, Mukherjee, Chandrani, additional, Bowers, Erin M., additional, Ahn, Young-Hoon, additional, Yoshida, Minoru, additional, Zhang, Jin, additional, Mahadevan, Louis C., additional, Meyers, David J., additional, Boeke, Jef D., additional, and Cole, Philip A., additional

Published
2012
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29. Virtual Ligand Screening of the p300/CBP Histone Acetyltransferase: Identification of a Selective Small Molecule Inhibitor

Author

Bowers, Erin M., primary, Yan, Gai, additional, Mukherjee, Chandrani, additional, Orry, Andrew, additional, Wang, Ling, additional, Holbert, Marc A., additional, Crump, Nicholas T., additional, Hazzalin, Catherine A., additional, Liszczak, Glen, additional, Yuan, Hua, additional, Larocca, Cecilia, additional, Saldanha, S. Adrian, additional, Abagyan, Ruben, additional, Sun, Yan, additional, Meyers, David J., additional, Marmorstein, Ronen, additional, Mahadevan, Louis C., additional, Alani, Rhoda M., additional, and Cole, Philip A., additional

Published
2010
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31. Stress-activated MAP Kinases in Chromatin and Transcriptional Complexes.

Author

Posas, Francesc, Nebreda, Angel R., Crump, Nicholas T., Han, Ya Ting, and Mahadevan, Louis C.

Abstract

Stress-activated MAP kinases (SAPKs) are activated by stressors or by certain physiological stimuli and mediate an intracellular response appropriate to the change in environment. Long-term adaptation requires reprogramming of transcription and one of the most significant actions of SAPK cascades is therefore induction of gene expression. SAPKs and their downstream kinases phosphorylate many chromatin-associated and transcription factors. Further, they can induce localised histone modification by regulating histone acetyltransferases and deacetylases. p38/SAPK2 also elicits phosphorylation of the nucleosomal proteins histone H3 and HMGN1 (previously HMG-14) via the downstream mitogen- and stress-stimulated kinases MSK1/2. Finally, recent evidence indicates a novel non-enzymatic SAPK function in transcriptional complexes, suggesting a more structural role. The yeast SAPK Hog1p is recruited to a proportion of its target genes on activation and localises beyond the promoter into coding regions. The observation that Hog1p interacts with elongating RNA polymerase II in addition to several transcriptional elongation factors has led to the suggestion that this SAPK may behave like an elongation factor at some target genes. The generality of this new function is discussed. [ABSTRACT FROM AUTHOR]

Published
2008
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