Laboratory of Nuclear Organization
We study how biomolecular condensates organize gene regulation
Our primary goal is to understand how the gene control machinery is organized within the nucleus. Many nuclear processes have been found to operate within dynamic local concentrations termed biomolecular condensates. We study how nuclear condensates form at specific genomic loci, how they function once formed, and how they are misappropriated in disease.
Condensates form by the ensemble weak-multivalent and structured interactions among RNA, DNA, and protein molecules, which enable high local concentrations at specific genomic loci. This provides a means to dynamically organize macromolecular resources, allowing the cell to create on-demand and reversible local concentrations of functionally related proteins.
We are specifically interested in investigating 1) the role of intrinsically disordered regions (IDRs) found on many transcription and chromatin factors in condensate formation, 2) how the combination of hard-wired DNA sequence and dynamically-regulated chromatin states work together to seed and scaffold condensates, and 3) how nuclear condensates dynamically regulate their composition to create specialized reaction centers.
Multivalency in DNA Sequence
and Chromatin States
Nuclear Condensate Specialization
Postdoc at Whitehead Institute/MIT
Ph.D. from Rockefeller University
B.S. from University of Rochester
Ph.D. from Illinois State University
M.S. from Illinois State University
B.A. from Arcadia University
Nancy De La Cruz
B.S. from Texas Woman's University
B.A. from Wellesley College
Reshma T Veettil
Ph.D. from National Centre for Biological Science (NCBS), TIFR
M.S. from Amrita Vishwa Vidyapeetham
B.S. from Amrita Vishwa Vidyapeetham
Ph.D. from Indian Institute of Technology - Delhi
M.S. from South Asian University
B.S. from University of Delhi
B.A. from University of Iowa
Previous lab members
Lyons H, Veettil RT, Pradhan P, Fornero C, De La Cruz N, Ito K, Eppert M, Roeder RG, Sabari BR. (2023). Functional partitioning of transcriptional regulators by patterned charge blocks. Cell 186
Eppert M, Sabari BR. (2022). Context is key: Modulated protein multivalency is disease. Molecular Cell 82, 3965-3967
Cantu Oliveros (Lyons) H, Sabari BR. (2021). Disordered and dead, but in good company: How a catalytically inactive UTX retains its function. Molecular Cell 18, 4577-4578.
Sabari BR. (2020). Biomolecular condensates and gene activation in development and disease. Developmental Cell 55, 84-96
Sabari BR, Dall’Agnese A, Young RA. (2020). Biomolecular condensates in the nucleus. Trends in Biochemical Sciences 45, 961-977
Klein IA*, Boija A*, Afeyan LK, Hawken SW, Fan M, Dall’Agnese A, Oksuz O, Henninger JE, Shrinivas K, Sabari BR, et al. (2020). Partitioning of cancer therapeutics in nuclear condensates. Science 368, 1386-1392
Zamudio A.V., Dall'Agnese A, Henninger JE, Manteiga JC, Afeyan LK, Hannett NM, Coffey, EL, Li CH, Oksuz O, Sabari BR, et al. (2019). Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes. Molecular Cell 76, 1-14.
Guo YE*, Manteiga JC*, Henninger JE, Sabari BR, Dall'Agnese A, et al. (2019). Pol II phosphorylation regulates a switch between transcriptional and splicing condensates. Nature 13, 1–6.
Shrinivas K*, Sabari BR*, Coffey EL, Klein IA, Boija A, Zamudio AV, Schuijers J, Hannett NM, Sharp PA, Young RA, Chakraborty A (2019). Enhancer Features that Drive Formation of Transcriptional Condensates. Molecular Cell 75, 549–561.
Boija A*, Klein IA*, Sabari BR, Dall’Agnese A, et al. (2018) Transcription factors activate genes through the phase separation capacity of their activation domains. Cell 176, 1842-1855.
Sabari BR*, Dall'Agnese A*, Boija A, Klein IA, et al. (2018) Coactivator condensation at super-enhancers links phase separation and gene control. Science 361
Sabari BR*, Zhang D*, Allis CD, Zhao Y. (2017) Metabolic regulation of gene expression through histone acylations. Nature Reviews Molecular Cell Biology 18, 90–101
Melo FR, Wallerman O, Paivandy A, Calounova G, Gustafson A-M, Sabari BR, Zabucchi G, Allis CD, Pejler G. (2017) Tryptase-catalyzed core histone truncation: a novel epigenetic regulatory mechanism in mast cells. J. Allergy Clin. Immunol 140, 474–485.
Bayliss J, Mukherjee P, Lu C, Jain SU, Chung C, Martinez D, Sabari BR, et al. (2016) Lowered H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas. Science Translational Medicine 23
Li Y*, Sabari BR*, Panchenko T*, Wen H, Zhao D, Guan H, Wan L, Huang H, Tang Z, Zhao Y, Roeder RG, Shi X, Allis CD, Li H. (2016) Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain. Molecular Cell 62, 181–93.
Sabari BR, Tang Z, Huang H, Yong-Gonzalez V, Molina H, Kong HE, Dai L, Shimada M, Cross JR, Zhao Y, Roeder RG, Allis CD. (2015) Intracellular Crotonyl-CoA Stimulates Transcription through p300-Catalyzed Histone Crotonylation. Molecular Cell 58, 203–15.
Huang H, Sabari BR, Garcia BA, Allis CD, Zhao Y. (2014) SnapShot: Histone Modifications. Cell 159
Dai L, Peng C, Montellier E, Lu Z, Chen Y, Ishii H, Debernardi A, Buchou T, Rousseaux S, Jin F, Sabari BR, Deng Z, Allis CD, Ren B, Khochbin S, Zhao Y. (2014) Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark. Nature Chemical Biology 10, 365–370.