Publication Title: 
Nature Chemical Biology

Cellular damage invoked by reactive oxygen species plays a key role in the pathobiology of cancer and aging. Forkhead box class O (FoxO) transcription factors are involved in various cellular processes including cell cycle regulation, apoptosis and resistance to reactive oxygen species, and studies in animal models have shown that these transcription factors are of vital importance in tumor suppression, stem cell maintenance and lifespan extension.

Dansen, Tobias B.
Smits, Lydia M. M.
van Triest, Miranda H.
de Keizer, Peter L. J.
van Leenen, Dik
Koerkamp, Marian Groot
Szypowska, Anna
Meppelink, Amanda
Brenkman, Arjan B.
Yodoi, Junji
Holstege, Frank C. P.
Burgering, Boudewijn M. T.
Publication Title: 
Nature Communications

A de novo G608G mutation in LMNA gene leads to Hutchinson-Gilford progeria syndrome. Mice lacking the prelamin A-processing metalloprotease, Zmpste24, recapitulate many of the progeroid features of Hutchinson-Gilford progeria syndrome. Here we show that A-type lamins interact with SUV39H1, and prelamin A/progerin exhibits enhanced binding capacity to SUV39H1, protecting it from proteasomal degradation and, consequently, increasing H3K9me3 levels. Depletion of Suv39h1 reduces H3K9me3 levels, restores DNA repair capacity and delays senescence in progeroid cells.

Liu, Baohua
Wang, Zimei
Zhang, Le
Ghosh, Shrestha
Zheng, Huiling
Zhou, Zhongjun
Publication Title: 
Aging Cell

Coordinated expression of mitochondrial and nuclear genes is required to maintain proper mitochondrial function. However, the precise mechanisms that ensure this coordination are not well defined. We find that signaling from mitochondria to the nucleus is influenced by mammalian target of rapamycin (mTOR) activity via changes in autophagy and p62/SQSTM1 turnover. Reducing mTOR activity increases autophagic flux, enhances mitochondrial membrane potential, reduces reactive oxygen species within the cell, and increases replicative life span.

Lerner, Chad
Bitto, Alessandro
Pulliam, Daniel
Nacarelli, Timothy
Konigsberg, Mina
Van Remmen, Holly
Torres, Claudio
Sell, Christian
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

A fundamental question in the basic biology of aging is whether there is a universal aging process. If indeed such a process exists, one would expect that it develops at a higher rate in short- versus long-lived species. We have quantitated pentosidine, a marker of glycoxidative stress in skin collagen from eight mammalian species as a function of age. A curvilinear increase was modeled for all species, and the rate of increase correlated inversely with maximum life-span.

Sell, D. R.
Lane, M. A.
Johnson, W. A.
Masoro, E. J.
Mock, O. B.
Reiser, K. M.
Fogarty, J. F.
Cutler, R. G.
Ingram, D. K.
Roth, G. S.
Monnier, V. M.
Publication Title: 
The Journal of Biological Chemistry

Elevated LDL-cholesterol is a risk factor for the development of cardiovascular disease. Thus, proper control of LDL-cholesterol homeostasis is critical for organismal health. Genetic analysis has identified PCSK9 (proprotein convertase subtilisin/kexin type 9) as a crucial gene in the regulation of LDL-cholesterol via control of LDL receptor degradation. Although biochemical characteristics and clinical implications of PCSK9 have been extensively investigated, epigenetic regulation of this gene is largely unknown.

Tao, Rongya
Xiong, Xiwen
DePinho, Ronald A.
Deng, Chu-Xia
Dong, X. Charlie
Publication Title: 
Journal of Neurochemistry

Glutamatergic signaling is regulated, in part, through differential expression of NMDA and AMPA/KA channel subunits and G protein-coupled metabotropic receptors. In human brain, region-specific expression patterns of glutamate receptor genes are maintained over the course of decades, suggesting a role for molecular mechanisms involved in long-term regulation of transcription, including methylation of lysine residues at histone N-terminal tails.

Stadler, Florian
Kolb, Gabriele
Rubusch, Lothar
Baker, Stephen P.
Jones, Edward G.
Akbarian, Schahram
Publication Title: 
Biological Psychiatry

Alterations in RNA levels are frequently reported in brain of subjects diagnosed with autism, schizophrenia, depression, and other psychiatric diseases, but it remains unclear whether the underlying molecular pathology involves changes in gene expression, as opposed to alterations in messenger RNA processing. Pre-clinical studies have revealed that stress, drugs, and a variety of other environmental factors lead to changes in RNA levels in brain via epigenetic mechanisms, including modification of histone proteins.

Akbarian, Schahram
Huang, Hsien-Sung
Publication Title: 
Schizophrenia Research

OBJECTIVE: Epigenetic changes are stable and long-lasting chromatin modifications that regulate genomewide and local gene activity. The addition of two methyl groups to the 9th lysine of histone 3 (H3K9me2) by histone methyltransferases (HMT) leads to a restrictive chromatin state, and thus reduced levels of gene transcription. Given the numerous reports of transcriptional down-regulation of candidate genes in schizophrenia, we tested the hypothesis that this illness can be characterized by a restrictive epigenome.

Chase, Kayla A.
Gavin, David P.
Guidotti, Alessandro
Sharma, Rajiv P.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Transcriptional dysregulation is an early feature of Huntington disease (HD). We observed gene-specific changes in histone H3 lysine 4 trimethylation (H3K4me3) at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective.

Vashishtha, Malini
Ng, Christopher W.
Yildirim, Ferah
Gipson, Theresa A.
Kratter, Ian H.
Bodai, Laszlo
Song, Wan
Lau, Alice
Labadorf, Adam
Vogel-Ciernia, Annie
Troncosco, Juan
Ross, Christopher A.
Bates, Gillian P.
Krainc, Dimitri
Sadri-Vakili, Ghazaleh
Finkbeiner, Steven
Marsh, J. Lawrence
Housman, David E.
Fraenkel, Ernest
Thompson, Leslie M.
Publication Title: 
In Vivo (Athens, Greece)

BACKGROUND/AIM: The aim of this study was to investigate the state of chromatin condensation in peripheral blood leukocytes of alcoholics, during the early detoxification period, in order to highlight structural modifications, indicating epigenetic mechanisms regulated by alcohol. MATERIALS AND METHODS: Blood samples were obtained from alcoholic patients, who were admitted for detoxification on an inpatient basis, and from healthy controls.

Piterou, Margarita Chrysanthou
Pantazidou, Ismini Kloukina
Havaki, Sophia
Liappas, John
Radovitch, Marietta Issidorides


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