Danny Reinberg, Ph.D.
Professor of Biochemistry
Investigator, Howard Hughes Medical Institute
Ph.D, 1982 Albert Einstein College of Medicine,
Bronx, New York
chromatin structure, Biochemistry, Gene regulation, Stem cell Biology and Ant Biology
Epigenetics, Transcription, RNA Polymerase II, Histones, Non-coding RNA
Smilow Research Institute
Department of Biochemistry
HHMI@New York University School of Medicine
522 First Avenue, 2nd Floor
New York, New York 10016
Office Tel: (212) 263-9036
Lab Tel: (212) 263-9033
Fax: (212) 263-9040
Our current focus is on the molecular mechanisms of epigenetics, that is, the extra-genetic information that gives rise to the different patterns of gene expression that distinguish different cells of an organism. Since all the cells of an individual contain identical DNA, the different patterns of genes they express come about, in part, by how tightly the different regions of the DNA are packaged. This packaging of the DNA can either be an obstacle to gene expression or can be a loose assemblage that allows RNA polymerase access to the DNA to be transcribed. Different regions of the genome are packaged differently to give rise to distinct tissues and this occurs during development. These patterns of gene expression are then maintained in adult cells and, importantly, this extra-genetic information is transferred to daughter cells after cell division so that the tissue specificity is again maintained.
One critical aspect of how this packaging is regulated involves specific modifications placed on the histone proteins around which the DNA is wrapped. The histones can be modified at their N-terminal tails and these modifications include acetyl-groups, phosphates and methyl-groups. In fact, some of these modifications can affect other modifications being placed on the same histone protein demonstrating the intricacies and dynamics inherent to the regulation of this process.
Of particular interest for our studies are the enzymes responsible for placing methyl modifications on lysine residues of histone proteins. Some methyl modifications appear to be very stable and therefore their presence might account for the heritability of patterned gene expression. We are studying the factors required to achieve higher-order genome structures as well as the regulation and capabilities of the enzymes that place methyl groups, and how and when they are targeted to different histones on the DNA.
Given that tumorigenesis is a prime example of misregulated gene expression patterns, studies of the molecular basis of epigenetics would pertain to aberrant as well as normal cellular identity. As an example, the levels of one of the histone lysine methyltransferases under study are up-regulated in later stages of prostate cancer, specifically when the cancer becomes metastatic. We are currently investigating the function of this histone lysine methyltransferase using mouse-model systems.
- SFMBT1 functions with LSD1 to regulate expression of canonical histone genes and chromatin-related factors. Zhang J, Bonasio R, Strino F, Kluger Y, Holloway JK, Modzelewski AJ, Cohen PE, Reinberg D. Genes Dev. 2013 Apr 1;27(7):749-66. doi: 10.1101/gad.210963.112. PMID: 23592795
- The role of PR-Set7 in replication licensing depends on Suv4-20h. Beck DB, Burton A, Oda H, Ziegler-Birling C, Torres-Padilla ME, Reinberg D.Genes Dev. 2012 Dec 1;26(23):2580-9. doi: 10.1101/gad.195636.112. Epub 2012 Nov 14. PMID: 23152447
- Asymmetrically modified nucleosomes.Voigt P, LeRoy G, Drury WJ 3rd, Zee BM, Son J, Beck DB, Young NL, Garcia BA, Reinberg D.Cell. 2012 Sep 28;151(1):181-93. doi: 10.1016/j.cell.2012.09.002. PMID: 23021224
- Genome-wide and caste-specific DNA methylomes of the ants Camponotus floridanus and Harpegnathos saltator. Bonasio R, Li Q, Lian J, Mutti NS, Jin L, Zhao H, Zhang P, Wen P, Xiang H, Ding Y, Jin Z, Shen SS, Wang Z, Wang W, Wang J, Berger SL, Liebig J, Zhang G, Reinberg D.Curr Biol. 2012 Oct 9;22(19):1755-64. doi: 10.1016/j.cub.2012.07.042. Epub 2012 Aug 9. PMID: 22885060
- L3MBTL2 Protein Acts in Concert with PcG Protein-Mediated Monoubiquitination of H2A to Establish a Repressive Chromatin Structure. Trojer P, Cao AR, Gao Z, Li Y, Zhang J, Xu X, Li G, Losson R, Erdjument-Bromage H, Tempst P, Farnham PJ, Reinberg D. (2011) Mol Cell. 42(4):438-50. PMID: 21596310
- The C-terminal domain of RNA polymerase II is modified by site-specific methylation. Sims RJ 3rd, Rojas LA, Beck D, Bonasio R, Schüller R, Drury WJ 3rd, Eick D, Reinberg D. (2011) Science. 332(6025):99-103. PMID: 21454787
- Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Kaneko S, Li G, Son J, Xu CF, Margueron R, Neubert TA, Reinberg D.Genes Dev. 2010 Dec 1;24(23):2615-20. doi: 10.1101/gad.1983810. PMID: 21123648
- Regulation of the histone H4 monomethylase PR-Set7 by CRL4(Cdt2)-mediated PCNA-dependent degradation during DNA damage. Oda H, Hübner MR, Beck DB, Vermeulen M, Hurwitz J, Spector DL, Reinberg D. (2010) Mol Cell. 40(3):364-76. PMID: 21035370
- Genomic comparison of the ants Camponotus floridanus and Harpegnathos saltator. Bonasio R, Zhang G, Ye C, Mutti NS, Fang X, Qin N, Donahue G, Yang P, Li Q, Li C, Zhang P, Huang Z, Berger SL, Reinberg D, Wang J, Liebig J. (2010)Science. 329(5995):1068-71. PMID: 20798317
- Highly compacted chromatin formed in vitro reflects the dynamics of transcription activation in vivo. Li G, Margueron R, Hu G, Stokes D, Wang YH, Reinberg D. (2010) Mol Cell. 38(1):41-53. PMID: 20385088
- Role of the polycomb protein EED in the propagation of repressive histone marks. Margueron R, Justin N, Ohno K, Sharpe ML, Son J, Drury WJ 3rd, Voigt P, Martin SR, Taylor WR, De Marco V, Pirrotta V, Reinberg D, Gamblin SJ. (2009) Nature. 461(7265):762-7. PMID: 19767730
- Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Margueron R, Li G, Sarma K, Blais A, Zavadil J, Woodcock CL, Dynlacht BD, Reinberg D. (2008) Mol Cell. 32(4):503-18. PMID: 19026781
- SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. Vaquero A, Scher M, Erdjument-Bromage H, Tempst P, Serrano L,Reinberg D. (2007) Nature. 450(7168):440-4. PMID: 18004385
- L3MBTL1, a histone-methylation-dependent chromatin lock. Trojer P, Li G, Sims RJ 3rd, Vaquero A, Kalakonda N, Boccuni P, Lee D, Erdjument-Bromage H, Tempst P, Nimer SD, Wang YH, Reinberg D. (2007) Cell. 129(5):915-28. PMID: 17540172