Thomas Jenuwein (born 1956) is a

German German(s) may refer to: * Germany, the country of the Germans and German things **Germania (Roman era) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizenship in Germany, see also Ge ...

scientist working in the fields of

epigenetics In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

biology,

gene regulation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wide ...

and

genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...

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 29 member states, two prospect member states, and one associate member state. EMBL was created in ...

, working on fos

oncogenes An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

in the laboratory of Rolf Müller and the

University of Heidelberg Heidelberg University, officially the Ruprecht Karl University of Heidelberg (; ), is a public university, public research university in Heidelberg, Baden-Württemberg, Germany. Founded in 1386 on instruction of Pope Urban VI, Heidelberg is List ...

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

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 The Max Planck Institute of Immunobiology and Epigenetics (German language, German: ''Max-Planck-Institut für Immunbiologie und Epigenetik'') in Freiburg im Breisgau, Freiburg, Germany is an interdisciplinary research institute that conducts bas ...

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 Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

is the physiological template of our

genetic information A nucleic acid sequence is a succession of Nucleobase, bases within the nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. This succession is denoted by a series of a set of five different letters that indicate the orde ...

, the

DNA double helix In molecular biology, the term double helix refers to the structure formed by double-stranded molecules of nucleic acids such as DNA. The double helical structure of a nucleic acid complex arises as a consequence of its secondary structure, a ...

. The basic subunits of

, the

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes ...

proteins, function in the packaging of the

and in controlling

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

through a variety of histone modifications. When Jenuwein started his

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 The SET domain is a protein domain that typically has methyltransferase activity. It was originally identified as part of a larger conserved region present in the ''Drosophila'' Trithorax protein and was subsequently identified in the ''Drosophi ...

, originally identified by the laboratory of Gunter Reuter. The

is present in Su(var)3–9, Enhancer of zeste and Trithorax proteins, all of which had been implicated in

epigenetic regulation In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...

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-t ...

modulated the distribution of

histone H3 Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal end, N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'b ...

phosphorylation during the

cell cycle The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...

in a

dependent manner. This insight, together with refined bioinformatic interrogation revealing a distant relationship of the

with plant methyltransferases, suggested the critical experiment: to test recombinant

for KMT activity on

substrates. This experiment revealed robust catalytic activity of the

of recombinant

to methylate

in vitro and was shown to be selective for the histone H3 lysine 9 position (

H3K9me3 H3K9me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation at the 9th lysine residue of the histone H3 protein and is often associated with heterochromatin. Nomenclature H3K9me ...

). This seminal discovery identified the first histone lysine methyltransferase for eukaryotic

.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 Overview Chromodomains are evolutionarily conserved protein domains found across a wide variety of eukaryotic species. Some chromodomain-containing genes have multiple alternative splicing isoforms that omit the chromodomain entirely. They are p ...

heterochromatin protein 1 The family of heterochromatin protein 1 (HP1) ("Chromobox Homolog", CBX) consists of highly conserved proteins, which have important functions in the cell nucleus. These functions include gene repression by heterochromatin formation, transcr ...

(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 continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a rol ...

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 Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segreg ...

defects and develop

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

. 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 (1861–1939) in Ingelheim am Rhein, Germany. As of 2018, Boehringer Ingelheim is one of the world's List of la ...

, 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 In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA ( transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from al ...

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 In biology, the epigenome of an organism is the collection of chemical changes to its DNA and histone proteins that affects when, where, and how the DNA is expressed; these changes can be passed down to an organism's offspring via transgenerat ...

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 In biology, the epigenome of an organism is the collection of chemical changes to its DNA and histone proteins that affects when, where, and how the DNA is expressed; these changes can be passed down to an organism's offspring via transgeneratio ...

. Genome-wide maps for Suv39h-dependent

marks and Hiseq RNA sequencing revealed a novel role for the Suv39h KMT in the silencing of repeat elements (e.g. LINE and ERV

retrotransposons Retrotransposons (also called Class I transposable elements) are transposable element, mobile elements which move in the host genome by converting their transcribed RNA into DNA through reverse transcription. Thus, they differ from Class II trans ...

) in mouse

embryonic stem cells Embryonic stem cells (ESCs) are Cell potency#Pluripotency, pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-Implantation (human embryo), implantation embryo. Human embryos reach the blastocyst stage 4� ...

. The demonstration that the pericentric major satellite repeats have embedded

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

(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

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, histone proteins and resembles thread wrapped around a bobbin, spool. The nucleosome ...

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

biology and

epigenetic In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...

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

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 (genetics), promoter, DNA methylati ...

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 A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most, if not ...

and the rDNA cluster and is a crucial mechanism for Polycomb- and Trithorax-mediated gene regulation. Histone lysine methylation marks also defined

bivalent chromatin Bivalent chromatin are segments of DNA, bound to histone proteins, that have both repressing and activating epigenetic regulators in the same region. These regulators work to enhance or silence the expression of genes. Since these regulators work ...

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 In biology, reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of histones. ...

have become possible. Since histone lysine methylation marks (as well as the other

modifications) are reversible, their enzymatic systems represent ideal targets for novel drug discovery programs that have greatly advanced

epigenetic therapy Epigenetic therapy refers to the use of drugs or other interventions to modify gene expression patterns, potentially treating diseases by targeting epigenetic mechanisms such as DNA methylation and histone modifications. Epigenetics is the stud ...

. The response of

to environmental signals and its possible

epigenetic inheritance Transgenerational epigenetic inheritance is the proposed transmission of epigenetic markers and modifications from one generation to multiple subsequent generations without altering the primary structure of DNA. Thus, the regulation of genes via ep ...

via the

germ line In biology and genetics, the germline is the population of a multicellular organism's cells that develop into germ cells. In other words, they are the cells that form gametes ( eggs and sperm), which can come together to form a zygote. They dif ...

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 The European Molecular Biology Organization (EMBO) is a professional, non-profit organization of more than 2,100 life scientists. Its goal is to promote research in life science and enable international exchange between scientists. It co-funds cour ...

Academia Europaea The Academia Europaea is a pan-European Academy of humanities, letters, law, and sciences. The Academia was founded in 1988 as a functioning Europe-wide Academy that encompasses all fields of scholarly inquiry. It acts as co-ordinator of Europe ...

, the

Austrian Academy of Sciences The Austrian Academy of Sciences (; ÖAW) is a legal entity under the special protection of the Republic of Austria. According to the statutes of the Academy its mission is to promote the sciences and humanities in every respect and in every fi ...

and the

American Academy of Arts and Sciences The American Academy of Arts and Sciences (The Academy) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and other ...

. He was awarded an Honorary Professorship at the

University of Vienna The University of Vienna (, ) is a public university, public research university in Vienna, Austria. Founded by Rudolf IV, Duke of Austria, Duke Rudolph IV in 1365, it is the oldest university in the German-speaking world and among the largest ...

(2003) and a co-opting professorship with appointment at the Medical Faculty of the

University of Freiburg The University of Freiburg (colloquially ), officially the Albert Ludwig University of Freiburg (), is a public university, public research university located in Freiburg im Breisgau, Baden-Württemberg, Germany. The university was founded in 1 ...

(2010). In 2005, he obtained the

Sir Hans Krebs Medal The Sir Hans Krebs Lecture and Medal is awarded annually by the Federation of European Biochemical Societies (FEBS) for outstanding achievements in Biochemistry and Molecular Biology or related sciences. It was endowed by the Lord Rank Centre fo ...

of the

FEBS The Federation of the European Biochemical Societies (FEBS) is an international scientific society promoting activities in biochemistry, molecular biology and related research areas in Europe and neighbouring regions. It was founded in 1964 and inc ...

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 in ...

of the

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

EMBO Embo or EMBO may refer to: *Embo, Taguig, a grouping of barangays in Taguig, Philippines * Embo (''Star Wars''), a ''Star Wars'' fictional character *Embo S.p.A., an Italian automotive manufacturer *Embo, Sutherland, a village in Highland, Scotland ...

* 2002–2007 Member

Faculty of 1000 F1000 (formerly "Faculty of 1000") is an open research publisher for scientists, scholars, and clinical researchers. F1000 offers a different research evaluation service from standard academic journals by offering peer-review after, rather than ...

(Nuclear Structure and Function) * 2003 Honorary Professorship in Epigenetics at

Vienna University The University of Vienna (, ) is a public university, public research university in Vienna, Austria. Founded by Rudolf IV, Duke of Austria, Duke Rudolph IV in 1365, it is the oldest university in the German-speaking world and among the largest ...

* 2005

Society * 2007

* 2010 Co-opting Professorship, Medical Faculty,

* 2013 Member of

* 2017 Elected corresponding member of the

* 2019 International Member of the

References

External links

Laboratory Thomas Jenuwein
at the

Max Planck Society The Max Planck Society for the Advancement of Science (; abbreviated MPG) is a formally independent non-governmental and non-profit association of German research institutes. Founded in 1911 as the Kaiser Wilhelm Society, it was renamed to the M ...

{{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