Danny Reinberg

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Danny Reinberg (born 1954) is a Chilean researcher and professor of Biochemistry.[1]  His major research focus areas include transcription factors, genetic transcription, histones, RNA Polymerase II, and Chromatin.[2]

Danny Reinberg
Born
Chile
EducationCatholic University (BS),
Albert Einstein College of Medicine (PhD)
Known forChromatin, Histones, Genomics, Pharmacology, RNA Polymerase II, Stem Cell Biology, Transcription Factors

Early life and education[]

Danny Reinberg was born in Santiago, Chile in 1954.[3] Reinberg spent his early life in Santiago where he attended The Kent School, graduating Upper School in 1971.[4] Next, Reinberg moved on to pursue a higher education at the Catholic University in Valparaiso, Chile.  Reinberg graduated from the University with a Bachelors in Science in 1977.[3] After completing his Bachelor's degree, Reinberg decided to move to The United States to pursue a postgraduate program.  Reinberg attended Albert Einstein College of Medicine in the Bronx, New York where he received his postdoctoral degree in 1982.  There, Reinberg worked as a graduate student under J. Hurwitz in the Department of Biology and Cancer.  To supplement his research, Reinberg also worked under R.G. Roeder at Rockefeller University in New York.[3]  Finally, at age 32, Danny Reinberg became a Professor in the Department of Biochemistry at the University of Medicine and Dentistry of New Jersey.  At age 40, Reinberg became a Distinguished University Professor and HHMI Investigator at Robert Wood Johnson Medical School in New Jersey.[3] Finally, in 2006, Reinberg moved his research to the New York University Langone School of Medicine where he is currently a Professor in the department of Biochemistry and Molecular Pharmacology.[1]  

Research[]

Over the course of his career thus far, Danny Reinberg has made a major impact on the scientific research of gene expression. Reinberg has co-authored well over 400 scholarly articles, and he averages over 3000 citations per year.[5] Reinberg also co-edited an educational textbook written to teach epigenetics.[6]

Perhaps Reinberg's major research focus is the regulation of gene expression in eukaryotes.  One of his long-term research goals is to determine how a gene gets transcribed, when it gets transcribed, and what controls this transcription.[7]  Reinberg works towards this goal by determining the criteria that facilitates or interrupts transcription as an overall mechanism of a complex gene organizational unit.[7]  

In his earliest years, Reinberg worked to research transcription factor EivF.  His research involving this factor concluded that affinity purified EivF can bind to the Eiv promoter, it is transcriptionally active, multiple factors can bind to the EivF recognition site, and EivF can bind to the gonadotropin and somatostatin cAMP responsive elements.[8]

When Reinberg completed his postdoctoral studies at Albert Einstein College, his research interest shifted to center around RNA Polymerase II.  Reinberg began researching the bases of RNA Polymerase II mediated transcription.[3] In 1991, Reinberg and his research team publicized an article summarizing their discovery of transcription factor IIF's role relating to RNA polymerase II and the preinitiation complex. This research concluded that IIF indeed mediates the association of RNA polymerase II with its associated promoter sequence that contains other transcription factors.[9]  Reinberg continued his studies regarding Polymerase II in a study conducted to determine the how the RNA Polymerase II complex associates with SRB and DNA repair proteins.  This research concluded that the junction of Polymerase II and yeast SRB proteins increases the activation of transcription as well as participates in DNA repair.[10]  Next, Reinberg worked with a team to research NAT, a complex found in humans that functions in transcription activation.[11]  This research proved that this complex is a subcomplex of the RNAPII holoenzyme.[11]  The team concluded that RNAPII is a transcription control panel that responds to signals of activation or repression of transcription.[11]

Reinberg then moved on to begin investigating Sin3, a corepressor.  His research team found that a human sin3-HDAC complex includes HDAC1, HDAC2, RbAp46, RbAp48, SAP30, and SAP18.[12]  In addition, this team discovered that the Sin3 complex is an important factor for growth suppression of p33ING1b.[12]

In 2003, Reinberg worked with a team to review the types of proteins that alter the structure and function of chromatin.  In addition, the team worked to research the role of chromatin in cell aging.  This comprehensive review of chromatin provides various intricate details about the material, as well as comparisons of scientific research techniques involving the material.[13]  This account concluded that chromatin metabolism is a key link in the study of cell aging.[13]

In 2007, Reinberg and a team of researchers worked to demonstrate that the malignant brain tumor protein L3MBTL1 is in a histone complex.  The team also found that the L3MBTL1/MBT domains compact nucleosome arrays that are highly dependent on certain histones and lysines.[14]  In addition, the team discovered that L3MBTL1 actually negatively regulates gene expression of genes that are regulated by E2F.[14]

A few years later, in 2011, Reinberg switched his focus back to RNA Polymerase II.  Through this research, he determined that RNA Polymerase II is methylated at a very specific arginine on the C-Terminal.  This conclusion suggests that the methylation of RNAPII is site specific and may discriminate the RNAPII recruited to different gene types.[15] This research continued, leading to Reinberg's publication involving FACT action during transcription through chromatin by RNA Polymerase II.  This study led to the suggestion that hFACT facilitates uncoiling of DNA from the histone octamer when it is combined with H2A/H2B dimers.  This discovery proved that this combination plays a major role in nucleosome survival during transcription.[16]

In 2016, Reinberg drifted from his usual research focus to begin studying cardiac differentiation. Reinberg coauthored a research article aiming to analyze ISL1 and JMJD3, and how they relate to the pathology of cardiac muscle.  Through this research, the team discovered that ISL1 directly regulates target genes involved in differentiation, recruits JMJD3 and promotes its demethylation, and pairs with JMJD3 to alter the cardiac epigenome.[17]

In 2018, the focus switched back to FACT as Reinberg began researching how this complex breaks the nucleosome and reorganizes it.  This study concluded that FACT plays a dual role in destabilizing the nucleosome while maintaining it's single nucleosome level.  The study stated that FACT contains two subunits- SSRP1 and SPT16.[18]  Reinberg's work showed that SSRP1 is responsible for maintaining the nucleosome integrity, while SPT16 is responsible for destabilizing the nucleosome.  These findings prove why the two FACT subunits communicate with each other to complete tasks.[18]  In addition, Reinberg was involved in the discovery that certain proteins may have the ability to replace FACT in certain situations.  Reinberg helped discover the idea that LEDGF and HGDF2 indeed degrade the nucleosome barrier involved in transcription of cells.  The study proved that these proteins are FACT-like factors, an important discovery being that FACT is not present in all tissues of the body.[19]

In 2019, Reinberg coauthored two publications related to nucleosomes and their role in the cell. The first publication focused on LEDGF and HDGF2 and their relief of the nucleosome induced barrier to transcription. This research focused on differentiated cells.  This study was conducted with the hopes of discovering another protein that could replace FACT if it is absent in the cell.  Both LEDGF and HDGF2 were discovered throughout this research and were determined to be present on most active genes.[19]  The research proved that both LEDGF and HDGF2 are competitive with FACT in that both isoforms allow RNAPII to transcribe through the nucleosome. A conclusion was drawn that LEDGF and HDGF2 may facilitate transcription of genes that have lower or nonexistent levels of FACT.[19]  The second study focused more on chromatin domains and how they may exhibit nucleosome segregation during replication of DNA.  This study aimed to answer the question of the fate of chromatins and their nucleosomes following DNA replication.  Reinberg and his team devised a way to track the nucleosomes after replication to be able to observe this fate.  Through this method, the team discovered that there was conservation in the recycling of certain intact parental nucleosomes within repressive chromatin domains, but not with active chromatin domains.[20]  These findings open up the door for future findings related to replication in that they answer the question of what types of nucleosomes are segregated and what types are re-distributed.[20]

Following his two publications in 2019, Reinberg continued his research on nucleosomes and published yet another study involving these structures.  After concluding the fact that certain nucleosomes face segregation following replication, Reinberg continued this research by studying how these nucleosomes relate to the inheritance of cellular identity.   This research concluded that there is still much to be learned regarding the segregation of parental tetramers involved in replication, but it is most likely that they do function as histone chaperones.[21]  Small advancements in research such as this study are the backbone of future findings, and it is likely that many more questions regarding developmental process will be scientifically answered in the coming years thanks to researchers like Danny Reinberg.[21]

Awards and Honors[]

References[]

  1. ^ a b "Internationally Renowned Researcher from NYU Langone Elected to the National Academy of Sciences". NYU Langone News. Retrieved 2021-04-15.
  2. ^ "Danny Reinberg". med.nyu.edu. Retrieved 2021-04-15.
  3. ^ a b c d e "Danny Reinberg". www.nasonline.org. Retrieved 2021-04-15.
  4. ^ "Danny Reinberg". www.facebook.com. Retrieved 2021-04-15.
  5. ^ "Danny Reinberg, Ph.D." scholar.google.com. Retrieved 2021-04-15.
  6. ^ "Danny Reinberg, PhD, Elected Member of Prestigious Institute of Medicine". www.newswise.com. Retrieved 2021-04-15.
  7. ^ a b "Research – Dr. Danny Reinberg Laboratory". Retrieved 2021-04-15.
  8. ^ Cortes P, Buckbinder L, Leza MA, Rak N, Hearing P, Merino A, Reinberg D (August 1988). "EivF, a factor required for transcription of the adenovirus EIV promoter, binds to an element involved in EIa-dependent activation and cAMP induction". Genes & Development. 2 (8): 975–90. doi:10.1101/gad.2.8.975. PMID 2844626.
  9. ^ Flores O, Lu H, Killeen M, Greenblatt J, Burton ZF, Reinberg D (November 1991). "The small subunit of transcription factor IIF recruits RNA polymerase II into the preinitiation complex". Proceedings of the National Academy of Sciences of the United States of America. 88 (22): 9999–10003. doi:10.1073/pnas.88.22.9999. PMC 52854. PMID 1946469.
  10. ^ Maldonado E, Shiekhattar R, Sheldon M, Cho H, Drapkin R, Rickert P, et al. (May 1996). "A human RNA polymerase II complex associated with SRB and DNA-repair proteins". Nature. 381 (6577): 86–9. doi:10.1038/381086a0. PMID 8609996.
  11. ^ a b c Sun X, Zhang Y, Cho H, Rickert P, Lees E, Lane W, Reinberg D (August 1998). "NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription". Molecular Cell. 2 (2): 213–22. doi:10.1016/s1097-2765(00)80131-8. PMID 9734358.
  12. ^ a b Kuzmichev A, Zhang Y, Erdjument-Bromage H, Tempst P, Reinberg D (February 2002). "Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1)". Molecular and Cellular Biology. 22 (3): 835–48. doi:10.1128/MCB.22.3.835-848.2002. PMC 133546. PMID 11784859.
  13. ^ a b Vaquero A, Loyola A, Reinberg D (April 2003). "The constantly changing face of chromatin". Science of Aging Knowledge Environment. 2003 (14): RE4. doi:10.1126/sageke.2003.14.re4. PMID 12844523.
  14. ^ a b Trojer P, Li G, Sims RJ, Vaquero A, Kalakonda N, Boccuni P, et al. (June 2007). "L3MBTL1, a histone-methylation-dependent chromatin lock". Cell. 129 (5): 915–28. doi:10.1016/j.cell.2007.03.048. PMID 17540172.
  15. ^ Sims RJ, Rojas LA, Beck DB, Bonasio R, Schüller R, Drury WJ, et al. (April 2011). "The C-terminal domain of RNA polymerase II is modified by site-specific methylation". Science. 332 (6025): 99–103. doi:10.1126/science.1202663. PMC 3773223. PMID 21454787.
  16. ^ Hsieh FK, Kulaeva OI, Patel SS, Dyer PN, Luger K, Reinberg D, Studitsky VM (May 2013). "Histone chaperone FACT action during transcription through chromatin by RNA polymerase II". Proceedings of the National Academy of Sciences of the United States of America. 110 (19): 7654–9. doi:10.1073/pnas.1222198110. PMC 3651417. PMID 23610384.
  17. ^ Wang Y, Li Y, Guo C, Lu Q, Wang W, Jia Z, et al. (August 2016). "ISL1 and JMJD3 synergistically control cardiac differentiation of embryonic stem cells". Nucleic Acids Research. 44 (14): 6741–55. doi:10.1093/nar/gkw301. PMC 5001586. PMID 27105846.
  18. ^ a b Chen P, Dong L, Hu M, Wang YZ, Xiao X, Zhao Z, et al. (July 2018). "Functions of FACT in Breaking the Nucleosome and Maintaining Its Integrity at the Single-Nucleosome Level". Molecular Cell. 71 (2): 284–293.e4. doi:10.1016/j.molcel.2018.06.020. PMID 30029006.
  19. ^ a b c LeRoy G, Oksuz O, Descostes N, Aoi Y, Ganai RA, Kara HO, et al. (October 2019). "LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription in differentiated cells". Science Advances. 5 (10): eaay3068. doi:10.1126/sciadv.aay3068. PMC 6774727. PMID 31616795.
  20. ^ a b Escobar TM, Oksuz O, Saldaña-Meyer R, Descostes N, Bonasio R, Reinberg D (October 2019). "Active and Repressed Chromatin Domains Exhibit Distinct Nucleosome Segregation during DNA Replication". Cell. 179 (4): 953–963.e11. doi:10.1016/j.cell.2019.10.009. PMID 31675501.
  21. ^ a b Escobar TM, Loyola A, Reinberg D (January 2021). "Parental nucleosome segregation and the inheritance of cellular identity". Nature Reviews. Genetics: 1–14. doi:10.1038/s41576-020-00312-w. PMID 33500558.
  22. ^ a b c d e "Danny Reinberg, Ph.D. '82 | Graduate Programs in the Biomedical Sciences | Albert Einstein College of Medicine". einsteinmed.org. Retrieved 2021-04-15.
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