Thomas Jenuwein (born 1956) is a German scientist working in the fields of epigenetics, chromatin biology, gene regulation and genome function.

Biography

Thomas Jenuwein received his Ph.D. in molecular biology in 1987 from the

EMBL The European Molecular Biology Laboratory (EMBL) is an intergovernmental organization dedicated to molecular biology research and is supported by 27 member states, two prospect states, and one associate member state. EMBL was created in 1974 and ...

, working on fos oncogenes in the laboratory of Rolf Müller and the University of Heidelberg and performed postdoctoral studies (1987-1993) on the immunoglobulin heavy chain (IgH) enhancer with Rudolf Grosschedl at the University of California San Francisco (UCSF). As an independent group leader (1993-2002) and then as a senior scientist (2002-2008) at the Research Institute of Molecular Pathology (IMP) in Vienna, he focused his research to chromatin regulation. Through this work, he and his team discovered the first histone lysine methyltransferase (KMT) that was published in 2000. He is currently director at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany where he heads the Department of Epigenetics."Home"
''www.ie-freiburg.mpg.de''. From 2004 to 2009, he coordinated the EU-funded network of excellence 'The Epigenome' , which connected more than 80 laboratories in Europe. Jenuwein is also co-editor of the first textbook on 'Epigenetics'"Epigenetics, Second Edition"
''cshlpress.com''. that was published by Cold Spring Harbor Laboratory Press in 2007 and 2015. He is an ambassador for the dissemination of Science and is actively engaged with public lectures
''HSTalks''.
''www.mpg.de''. and radio and TV documentations"Media Library"
''www.ie-freiburg.mpg.de''.
''WDR Nachrichten''. 1 July 2016. to inform lay audiences about 'Epigenetics'.

Career and research

Chromatin is the physiological template of our genetic information, the DNA double helix. The basic subunits of chromatin, the histone proteins, function in the packaging of the DNA double helix and in controlling

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

through a variety of histone modifications. When Jenuwein started his chromatin work in late 1993, no enzymes for histone modifications were known. He and his team cloned and characterized mammalian orthologs of dominant ''Drosophila'' PEV modifier factors containing the evolutionarily conserved SET domain, originally identified by the laboratory of Gunter Reuter. The SET domain is present in Su(var)3–9,

Enhancer of zeste Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme (EC 2.1.1.43) encoded by gene, that participates in histone methylation and, ultimately, transcriptional repression. EZH2 catalyzes the addition of methyl group ...

and

Trithorax Trithorax-group proteins (TrxG) are a heterogeneous collection of proteins whose main action is to maintain gene expression. They can be categorized into three general classes based on molecular function: # histone-modifying TrxG proteins # chroma ...

proteins, all of which had been implicated in

epigenetic regulation In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

without evidence of enzymatic activity. Overexpression of human

SUV39H1 Histone-lysine N-methyltransferase SUV39H1 is an enzyme that in humans is encoded by the ''SUV39H1'' gene. Function This gene is a member of the suppressor of variegation 3-9 homolog family and encodes a protein with a chromodomain and a C-ter ...

modulated the distribution of histone H3 phosphorylation during the cell cycle in a SET domain dependent manner. This insight, together with refined bioinformatic interrogation revealing a distant relationship of the SET domain with plant methyltransferases, suggested the critical experiment: to test recombinant

for KMT activity on histone substrates. This experiment revealed robust catalytic activity of the SET domain of recombinant

to methylate histone H3 in vitro and was shown to be selective for the histone H3 lysine 9 position ( H3K9me3). This seminal discovery identified the first histone lysine methyltransferase for eukaryotic chromatin.Pathology, Research Institute of Molecular
"Alumni Stories , Testimonials , Research Institute of Molecular Pathology (IMP)"
''The Research Institute of Molecular Pathology''. An important follow-up discovery was to show that SUV39H1-mediated H3K9 methylation generates a binding site for the chromodomain of heterochromatin protein 1 (HP1). Together, these landmark findings established a biochemical pathway for the definition of

heterochromatin Heterochromatin is a tightly packed form of DNA or '' condensed DNA'', which comes in multiple varieties. These varieties lie on a continue between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a role ...

and characterized Suv39h-dependent H3K9me3 as a central epigenetic modification for the repression of transcriptional activity. The in vivo function of the Suv39h KMT was demonstrated by the analysis of Suv39h double-null mice, which display chromosome segregation defects and develop leukemia. Together with

Boehringer Ingelheim C.H. Boehringer Sohn AG & Co. is the parent company of the Boehringer Ingelheim group, which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein, Germany. As of 2018, Boehringer Ingelheim is one of the world's largest pharmaceutical ...

, he identified the first small molecule inhibitor for KMT enzymes via screening of a chemical library. During the following years, Jenuwein then addressed the function of

towards transcriptional regulation and

genomic organization 300px, Genome sizes and corresponding composition of six major model organisms as pie charts. The increase in genome size correlates with the vast expansion of noncoding (i.e., intronic, intergenic, and interspersed repeat sequences) and repeat DN ...

, with a particular focus on the analysis of the non-coding genome. An initial map of the mouse epigenome was established by a cluster analysis of repressive histone modifications across repeat sequences and provided an important framework well ahead of the deep-sequencing advances in the profiling of epigenomes. Genome-wide maps for Suv39h-dependent H3K9me3 marks and Hiseq RNA sequencing revealed a novel role for the Suv39h KMT in the

silencing Silencing is a visual illusion in which a set of objects that change iluminancehueretrotransposons) in mouse embryonic stem cells. The demonstration that the pericentric major satellite repeats have embedded transcription factor (TF) binding sites that are relevant for TF-mediated recruitment of Suv39h enzymes has provided a general targeting mechanism for the formation of

. Most recent work has identified that repeat RNA transcripts from the major satellite repeats largely remain chromatin associated and form an RNA-

nucleosome A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamen ...

scaffold that is supported by RNA:DNA hybrids.

Significance and impact

The impact of the discovery of the first KMT and its associated functions has been so broad that it stimulated novel lines of research spanning nearly all aspects of chromatin biology and

epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

control for both basic and applied questions. The definition of

by the SUV39H1-H3K9me3-HP1 system has proven to be valid across nearly all model organisms. It allowed the functional dissection between histone and

DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...

and integrated the RNAi silencing pathway with H3K9 methylation. Histone lysine methylation has opened molecular insights for the organization of the inactive X chromosome, telomeres and the rDNA cluster and is a crucial mechanism for Polycomb- and

-mediated gene regulation. Histone lysine methylation marks also defined bivalent chromatin in embryonic stem cells and are instructive chromatin modifications that are used for epigenomic profiling in normal vs. diseased cells. They were also a crucial prerequisite for the later discoveries of histone demethylases (KDM). With all of these mechanistic insights, novel approaches in cancer biology, complex human disorders, cell senescence and reprogramming have become possible. Since histone lysine methylation marks (as well as the other histone modifications) are reversible, their enzymatic systems represent ideal targets for novel drug discovery programs that have greatly advanced epigenetic therapy. The response of chromatin to environmental signals and its possible

epigenetic inheritance Transgenerational epigenetic inheritance is the transmission of epigenetic markers from one organism to the next (i.e., from parent to child) that affects the traits of offspring without altering the primary structure of DNA (i.e. the sequence of ...

via the germ line is most likely also regulated, at least in part, by histone lysine methylation.

Honors and awards

Jenuwein is a member of several learned societies, such as the European Molecular Biology Organization, Academia Europaea, the Austrian Academy of Sciences and the American Academy of Arts and Sciences. He was awarded an Honorary Professorship at the University of Vienna (2003) and a co-opting professorship with appointment at the Medical Faculty of the University of Freiburg (2010). In 2005, he obtained the Sir Hans Krebs Medal of the FEBS Society and in 2007 the

Erwin Schrödinger Prize The Erwin Schrödinger Prize (German: Erwin Schrödinger-Preis) is an annual award presented by the Austrian Academy of Sciences for lifetime achievement by Austrians in the fields of mathematics and natural sciences. The prize was established i ...

of the Austrian Academy of Sciences. * 1990–1993 Special fellow of the Leukemia Society of America * 2002 Elected member of

EMBO Embo ( gd, Eurabol, IPA: �iaɾəpɔɫ̪ is a village in the Highland Council Area in Scotland and the former postal county of Sutherland, about north-northeast of Dornoch. On 16 July 1988, Embo declared itself independent from the rest of the ...

* 2002–2007 Member Faculty of 1000 (Nuclear Structure and Function) * 2003 Honorary Professorship in Epigenetics at

Vienna University The University of Vienna (german: Universität Wien) is a public university, public research university located in Vienna, Austria. It was founded by Rudolf IV, Duke of Austria, Duke Rudolph IV in 1365 and is the oldest university in the Geogra ...

* 2005 Sir Hans Krebs Medal of FEBS Society * 2007

, Austrian Academy of Sciences * 2010 Co-opting Professorship, Medical Faculty, University of Freiburg * 2013 Member of Academia Europaea * 2017 Elected corresponding member of the Austrian Academy of Sciences * 2019 International Member of the American Academy of Arts and Sciences

References

External links

Laboratory Thomas Jenuwein
at the Max Planck Institute of Immunobiology and Epigenetics *

Max Planck Society The Max Planck Society for the Advancement of Science (german: Max-Planck-Gesellschaft zur Förderung der Wissenschaften e. V.; abbreviated MPG) is a formally independent non-governmental and non-profit association of German research institutes. ...

{{DEFAULTSORT:Jenuwein, Thomas Max Planck Society people 1956 births Living people German geneticists People from Lohr am Main Members of the European Molecular Biology Organization Members of the Austrian Academy of Sciences Fellows of the American Academy of Arts and Sciences Academic staff of the University of Freiburg Max Planck Institute directors Heidelberg University alumni