Altered telomere homeostasis and resistance to skin carcinogenesis in Suv39h1 transgenic mice

Cell Cycle
Eleonora PettiStefan Schoeftner

Abstract

The Suv39h1 and Suv39h2 H3K9 histone methyltransferases (HMTs) have a conserved role in the formation of constitutive heterochromatin and gene silencing. Using a transgenic mouse model system we demonstrate that elevated expression of Suv39h1 increases global H3K9me3 levels in vivo. More specifically, Suv39h1 overexpression enhances the imposition of H3K9me3 levels at constitutive heterochromatin at telomeric and major satellite repeats in primary mouse embryonic fibroblasts. Chromatin compaction is paralleled by telomere shortening, indicating that telomere length is controlled by H3K9me3 density at telomeres. We further show that increased Suv39h1 levels result in an impaired clonogenic potential of transgenic epidermal stem cells and Ras/E1A transduced transgenic primary mouse embryonic fibroblasts. Importantly, Suv39h1 overexpression in mice confers resistance to a DMBA/TPA induced skin carcinogenesis protocol that is characterized by the accumulation of activating H-ras mutations. Our results provide genetic evidence that Suv39h1 controls telomere homeostasis and mediates resistance to oncogenic stress in vivo. This identifies Suv39h1 as an interesting target to improve oncogene induced senescence in premalignant lesions.

References

Mar 13, 1999·The Journal of Biological Chemistry·A C LeeT Finkel
Aug 3, 2001·Nature·S J NielsenT Kouzarides
Nov 12, 2002·The EMBO Journal·Isabel García-CaoManuel Serrano
Nov 11, 2003·Nature·Fabrizio d'Adda di FagagnaStephen P Jackson
Apr 7, 2004·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Simon R W L Chan, Elizabeth H Blackburn
Aug 5, 2005·Nature·Manuel ColladoManuel Serrano
Aug 5, 2005·Nature·Melanie BraigClemens A Schmitt
Aug 5, 2005·Nature·Chrysiis MichaloglouDaniel S Peeper
Sep 2, 2005·Nature Reviews. Genetics·Maria A Blasco
Dec 1, 2006·Nature·Raffaella Di MiccoFabrizio d'Adda di Fagagna
Jan 20, 2007·Genes & Development·Raquel BlancoMaría A Blasco
Jan 24, 2007·Nature Genetics·Roberta BenettiMaría A Blasco
Mar 17, 2007·Nature Reviews. Genetics·María A Blasco
Feb 20, 2008·Genes & Development·Ignacio FloresMaría A Blasco
Jul 7, 2009·Annual Review of Cell and Developmental Biology·Barna D FodorThomas Jenuwein
May 31, 2014·Cancer Research·Roberto DinamiStefan Schoeftner

❮ Previous
Next ❯

Citations

Jun 9, 2015·Cell Reports·Jan-Philipp Mallm, Karsten Rippe
Aug 24, 2017·Environmental and Molecular Mutagenesis·Juliana Carvalho Alves-SilvaFelipe Saldanha-Araujo
Dec 28, 2017·Journal of Dermatological Science·Kanad GhoshBrian C Capell

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
confocal microscopy
immunoprecipitation
ChIP
PCR
transgenics

Software Mentioned

Metamorph
ImageJ

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.