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48 results
2024
Rogers JM, Mimoso CA, Martin BJE, Martin AP, Aster JC, Adelman K, Blacklow SC. Notch induces transcription by stimulating release of paused RNA polymerase II.
Genes & Development. 2024;
Rogers JM, Mimoso CA, Martin BJE, Martin AP, Aster JC, Adelman K, Blacklow SC. Notch induces transcription by stimulating release of paused RNA polymerase II.
Genes & Development. 2024;
Notch proteins undergo ligand-induced proteolysis to release a nuclear effector that influences a wide range of cellular processes by regulating transcription. Despite years of study, however, how Notch induces the transcription of its target genes...
Fleming TJ, Antoszewski M, Lambo S, Gundry MC, Piussi R, Wahlster L, Shah S, Reed FE, Dong KD, Paulo JA, Gygi SP, Mimoso C, Goldman SR, Adelman K, Perry JA, Pikman Y, Stegmaier K, Barrachina MN, Machlus KR, Hovestadt V, Arruda A, Minden MD, Voit RA, Sankaran VG. CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias.
bioRxiv. 2024;:2024.12.30.630680.
Fleming TJ, Antoszewski M, Lambo S, Gundry MC, Piussi R, Wahlster L, Shah S, Reed FE, Dong KD, Paulo JA, Gygi SP, Mimoso C, Goldman SR, Adelman K, Perry JA, Pikman Y, Stegmaier K, Barrachina MN, Machlus KR, Hovestadt V, Arruda A, Minden MD, Voit RA, Sankaran VG. CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias.
bioRxiv. 2024;:2024.12.30.630680.
Acute myeloid leukemias (AMLs) have an overall poor prognosis with many high-risk cases co-opting stem cell gene regulatory programs, yet the mechanisms through which this occurs remain poorly understood. Increased expression of the stem cell...
Altıntaş UB, Seo JH, Giambartolomei C, Ozturan D, Fortunato BJ, Nelson GM, Goldman SR, Adelman K, Hach F, Freedman ML, Lack NA. Decoding the epigenetics and chromatin loop dynamics of androgen receptor-mediated transcription.
Nature Communications. 2024;15:9494.
Altıntaş UB, Seo JH, Giambartolomei C, Ozturan D, Fortunato BJ, Nelson GM, Goldman SR, Adelman K, Hach F, Freedman ML, Lack NA. Decoding the epigenetics and chromatin loop dynamics of androgen receptor-mediated transcription.
Nature Communications. 2024;15:9494.
Androgen receptor (AR)-mediated transcription plays a critical role in development and prostate cancer growth. AR drives gene expression by binding to thousands of cis-regulatory elements (CRE) that loop to hundreds of target promoters. With multiple CREs...
Tufan T, Comertpay G, Villani A, Nelson GM, Terekhova M, Kelley S, Zakharov P, Ellison RM, Shpynov O, Raymond M, Sun J, Chen Y, Bockelmann E, Stremska M, Peterson LW, Boeckaerts L, Goldman SR, Etchegaray I, Artyomov MN, Peri F, Ravichandran KS. Rapid unleashing of macrophage efferocytic capacity via transcriptional pause release.
Nature. 2024;628:408–415.
Tufan T, Comertpay G, Villani A, Nelson GM, Terekhova M, Kelley S, Zakharov P, Ellison RM, Shpynov O, Raymond M, Sun J, Chen Y, Bockelmann E, Stremska M, Peterson LW, Boeckaerts L, Goldman SR, Etchegaray I, Artyomov MN, Peri F, Ravichandran KS. Rapid unleashing of macrophage efferocytic capacity via transcriptional pause release.
Nature. 2024;628:408–415.
During development, inflammation or tissue injury, macrophages may successively engulf and process multiple apoptotic corpses via efferocytosis to achieve tissue homeostasis1. How macrophages may rapidly adapt their transcription to achieve continuous...
Zhao J, Cato LD, Arora UP, Bao EL, Bryant SC, Williams N, Jia Y, Goldman SR, Nangalia J, Erb MA, Vos SM, Armstrong SA, Sankaran VG. Inherited blood cancer predisposition through altered transcription elongation.
Cell. 2024;187:642–658.e19.
Zhao J, Cato LD, Arora UP, Bao EL, Bryant SC, Williams N, Jia Y, Goldman SR, Nangalia J, Erb MA, Vos SM, Armstrong SA, Sankaran VG. Inherited blood cancer predisposition through altered transcription elongation.
Cell. 2024;187:642–658.e19.
Despite advances in defining diverse somatic mutations that cause myeloid malignancies, a significant heritable component for these cancers remains largely unexplained. Here, we perform rare variant association studies in a large population cohort to...
Thivierge C, Bellefeuille M, Diwan SS, Dyakov BJA, Leventis R, Perron G, Najafabadi HS, Gravel SP, Gingras AC, Duchaine TF. Paraspeckle-independent co-transcriptional regulation of nuclear microRNA biogenesis by SFPQ.
Cell Reports. 2024;43.
Thivierge C, Bellefeuille M, Diwan SS, Dyakov BJA, Leventis R, Perron G, Najafabadi HS, Gravel SP, Gingras AC, Duchaine TF. Paraspeckle-independent co-transcriptional regulation of nuclear microRNA biogenesis by SFPQ.
Cell Reports. 2024;43.
Erickson EC, You I, Perry G, Dugourd A, Donovan KA, Crafter C, Johannes JW, Williamson S, Moss JI, Ros S, Ziegler RE, Barry ST, Fischer ES, Gray NS, Madsen RR, Toker A. Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation.
Science Signaling. 2024;17:eadf2670.
Erickson EC, You I, Perry G, Dugourd A, Donovan KA, Crafter C, Johannes JW, Williamson S, Moss JI, Ros S, Ziegler RE, Barry ST, Fischer ES, Gray NS, Madsen RR, Toker A. Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation.
Science Signaling. 2024;17:eadf2670.
More than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a...
Fisher RJ, Park K, Lee K, Pinjusic K, Vanasse A, Ennis CS, Ficcaro S, Marto J, Stransky S, Duke-Cohan J, Geethadevi A, Raabe E, Sidoli S, Hicks CW, Keskin DB, Wu CJ, Cole PA, Alani RM. CoREST Complex Inhibition Alters RNA Splicing to Promote Neoantigen Expression and Enhance Tumor Immunity.
bioRxiv. 2024;:2024.12.12.627852.
Fisher RJ, Park K, Lee K, Pinjusic K, Vanasse A, Ennis CS, Ficcaro S, Marto J, Stransky S, Duke-Cohan J, Geethadevi A, Raabe E, Sidoli S, Hicks CW, Keskin DB, Wu CJ, Cole PA, Alani RM. CoREST Complex Inhibition Alters RNA Splicing to Promote Neoantigen Expression and Enhance Tumor Immunity.
bioRxiv. 2024;:2024.12.12.627852.
Epigenetic complexes tightly regulate gene expression and colocalize with RNA splicing machinery; however, the consequences of these interactions are uncertain. Here, we identify unique interactions of the CoREST repressor complex with RNA splicing...
Trzaskoma P, Jung S, Pękowska A, Bohrer CH, Wang X, Naz F, Dell’Orso S, Dubois WD, Olivera A, Vartak SV, Zhao Y, Nayak S, Overmiller A, Morasso MI, Sartorelli V, Larson DR, Chow CC, Casellas R, O’Shea JJ. 3D chromatin architecture, BRD4, and Mediator have distinct roles in regulating genome-wide transcriptional bursting and gene network.
Science Advances. 2024;10:eadl4893.
Trzaskoma P, Jung S, Pękowska A, Bohrer CH, Wang X, Naz F, Dell’Orso S, Dubois WD, Olivera A, Vartak SV, Zhao Y, Nayak S, Overmiller A, Morasso MI, Sartorelli V, Larson DR, Chow CC, Casellas R, O’Shea JJ. 3D chromatin architecture, BRD4, and Mediator have distinct roles in regulating genome-wide transcriptional bursting and gene network.
Science Advances. 2024;10:eadl4893.
Discontinuous transcription is evolutionarily conserved and a fundamental feature of gene regulation; yet, the exact mechanisms underlying transcriptional bursting are unresolved. Analyses of bursting transcriptome-wide have focused on the role of cis...
2023
Rambout X, Cho H, Blanc R, Lyu Q, Miano JM, Chakkalakal JV, Nelson GM, Yalamanchili HK, Adelman K, Maquat LE. PGC-1α senses the CBC of pre-mRNA to dictate the fate of promoter-proximally paused RNAPII.
Molecular Cell. 2023;83(2):186–202.e11.
Rambout X, Cho H, Blanc R, Lyu Q, Miano JM, Chakkalakal JV, Nelson GM, Yalamanchili HK, Adelman K, Maquat LE. PGC-1α senses the CBC of pre-mRNA to dictate the fate of promoter-proximally paused RNAPII.
Molecular Cell. 2023;83(2):186–202.e11.
PGC-1α is well established as a metazoan transcriptional coactivator of cellular adaptation in response to stress. However, the mechanisms by which PGC-1α activates gene transcription are incompletely understood. Here, we report that PGC-1α serves as a...
Spencley AL, Bar S, Swigut T, Flynn RA, Lee CH, Chen LF, Bassik MC, Wysocka J. Co-transcriptional genome surveillance by HUSH is coupled to termination machinery.
Molecular Cell. 2023;83(10):1623–1639.e8.
Spencley AL, Bar S, Swigut T, Flynn RA, Lee CH, Chen LF, Bassik MC, Wysocka J. Co-transcriptional genome surveillance by HUSH is coupled to termination machinery.
Molecular Cell. 2023;83(10):1623–1639.e8.
The HUSH complex recognizes and silences foreign DNA such as viruses, transposons, and transgenes without prior exposure to its targets. Here, we show that endogenous targets of the HUSH complex fall into two distinct classes based on the presence or...
Townley BA, Buerer L, Tsao N, Bacolla A, Mansoori F, Rusanov T, Clark NE, Goodarzi N, Schmidt N, Srivatsan SN, Sun H, Sample RA, Brickner JR, McDonald D, Tsai MS, Walter MJ, Wozniak DF, Holehouse AS, Pena V, Tainer JA, Fairbrother WG, Mosammaparast N. A functional link between lariat debranching enzyme and the intron-binding complex is defective in non-photosensitive trichothiodystrophy.
Molecular Cell. 2023;83(13):2258–2275.e11.
Townley BA, Buerer L, Tsao N, Bacolla A, Mansoori F, Rusanov T, Clark NE, Goodarzi N, Schmidt N, Srivatsan SN, Sun H, Sample RA, Brickner JR, McDonald D, Tsai MS, Walter MJ, Wozniak DF, Holehouse AS, Pena V, Tainer JA, Fairbrother WG, Mosammaparast N. A functional link between lariat debranching enzyme and the intron-binding complex is defective in non-photosensitive trichothiodystrophy.
Molecular Cell. 2023;83(13):2258–2275.e11.
The pre-mRNA life cycle requires intron processing; yet, how intron-processing defects influence splicing and gene expression is unclear. Here, we find that TTDN1/MPLKIP, which is encoded by a gene implicated in non-photosensitive trichothiodystrophy (NP...