Homeodomain Proteins

Publication Title: 
Gerontology

What aging process is delayed by calorie restriction (CR) and mutations that produce long-lived dwarf mice? From 1935 until 1996, CR was the only option for increasing the maximum lifespan of laboratory rodents. In 1996, the mutation producing the Ames dwarf mouse (Prop-1(-/-)) was reported to increase lifespan. Since 1996, other gene mutations that cause dwarfism or lower body weight have been reported to increase the lifespan of mice. The recent discovery of long-lived mutant dwarf mice provides an opportunity to investigate common features between CR and dwarf models.

Author(s): 
McKee Alderman, J.
DePetrillo, Michael A.
Gluesenkamp, Angela M.
Hartley, Antonia C.
Verhoff, S. Veronica
Zavodni, Katherine L.
Combs, Terry P.
Publication Title: 
Aging Cell

Among the notable trends seen in this year's highlights in mammalian aging research is an awakening of interest in the assessment of age-related measures of mouse health in addition to the traditional focus on longevity. One finding of note is that overexpression of telomerase extended life and improved several indices of health in mice that had previously been genetically rendered cancer resistant. In another study, resveratrol supplementation led to amelioration of several degenerative conditions without affecting mouse lifespan.

Author(s): 
Austad, Steven
Publication Title: 
Translational Psychiatry

The elucidation of epigenetic alterations in the autism brain has potential to provide new insights into the molecular mechanisms underlying abnormal gene expression in this disorder. Given strong evidence that engrailed-2 (EN-2) is a developmentally expressed gene relevant to cerebellar abnormalities and autism, the epigenetic evaluation of this candidate gene was undertaken in 26 case and control post-mortem cerebellar samples. Assessments included global DNA methylation, EN-2 promoter methylation, EN-2 gene expression and EN-2 protein levels.

Author(s): 
James, S. J.
Shpyleva, Svitlana
Melnyk, Stepan
Pavliv, Oleksandra
Pogribny, I. P.
Publication Title: 
Stem Cells Translational Medicine

Recent advances in somatic cell reprogramming have highlighted the plasticity of the somatic epigenome, particularly through demonstrations of direct lineage reprogramming of adult mouse and human fibroblasts to induced pluripotent stem cells (iPSCs) and induced neurons (iNs) under defined conditions. However, human cells appear to be less plastic and have a higher epigenetic hurdle for reprogramming to both iPSCs and iNs. Here, we show that SH2B adaptor protein 1?

Author(s): 
Hsu, Yi-Chao
Chen, Su-Liang
Wang, Ya-Jean
Chen, Yun-Hsiang
Wang, Dan-Yen
Chen, Linyi
Chen, Chia-Hsiang
Chen, Hwei-Hsien
Chiu, Ing-Ming
Publication Title: 
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences

This paper presents a review of recent work on the role that two epigenetic-related systems may play in information processing mechanisms in the brain. The first consists of exosomes that transport epigenetic-related molecules between neurons. The second consists of homeoproteins like Otx2 that carry information from sense organs to primary sensory cortex. There is developing evidence that presynaptic neurons may be able to modulate the fine microanatomical structure in the postsynaptic neuron.

Author(s): 
Edelstein, Lawrence
Smythies, John
Publication Title: 
Translational Psychiatry

Epigenetic mechanisms regulate programmed gene expression during prenatal neurogenesis and serve as a mediator between genetics and environment in postnatal life. The recent discovery of 5-hydroxymethylcytosine (5-hmC), with highest concentration in the brain, has added a new dimension to epigenetic regulation of neurogenesis and the development of complex behavior disorders. Here, we take a candidate gene approach to define the role 5-hmC in Engrailed-2 (EN-2) gene expression in the autism cerebellum.

Author(s): 
James, S. J.
Shpyleva, S.
Melnyk, S.
Pavliv, O.
Pogribny, I. P.
Publication Title: 
Human Molecular Genetics

To investigate epigenetic contributions to Huntington's disease (HD) pathogenesis, we carried out genome-wide mapping of the transcriptional mark, trimethyl-histone H3-lysine 4 (H3K4me3) in neuronal nuclei extracted from prefrontal cortex of HD cases and controls using chromatin immunoprecipitation followed by deep-sequencing.

Author(s): 
Bai, Guang
Cheung, Iris
Shulha, Hennady P.
Coelho, Joana E.
Li, Ping
Dong, Xianjun
Jakovcevski, Mira
Wang, Yumei
Grigorenko, Anastasia
Jiang, Yan
Hoss, Andrew
Patel, Krupal
Zheng, Ming
Rogaev, Evgeny
Myers, Richard H.
Weng, Zhiping
Akbarian, Schahram
Chen, Jiang-Fan
Publication Title: 
The Journal of Comparative Neurology

The development of the cortex is an elaborate process that integrates a plethora of finely tuned molecular processes ranging from carefully regulated gradients of transcription factors, dynamic changes in the chromatin landscape, or formation of protein complexes to elicit and regulate transcription. Combined with cellular processes such as cell type specification, proliferation, differentiation, and migration, all of these developmental processes result in the establishment of an adult mammalian cortex with its typical lamination and regional patterning.

Author(s): 
Ypsilanti, AthÈna R.
Rubenstein, John L. R.
Publication Title: 
Experimental Neurology

Among several genetic mutations known to cause amyotrophic lateral sclerosis (ALS), a hexanucleotide repeat expansion in the C9orf72 gene is the most common. In approximately 30% of C9orf72-ALS cases, 5-methylcytosine (5mC) levels within the C9orf72 promoter are increased, resulting in a modestly attenuated phenotype. The developmental timing of C9orf72 promoter hypermethylation and the reason why it occurs in only a subset of patients remain unknown.

Author(s): 
Esanov, Rustam
Belle, Kinsley C.
van Blitterswijk, Marka
Belzil, Veronique V.
Rademakers, Rosa
Dickson, Dennis W.
Petrucelli, Leonard
Boylan, Kevin B.
Dykxhoorn, Derek M.
Wuu, Joanne
Benatar, Michael
Wahlestedt, Claes
Zeier, Zane
Publication Title: 
Epigenetics

Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val(66)Met), which creates or abolishes a CpG dinucleotide for DNA methylation.

Author(s): 
Ursini, Gianluca
Cavalleri, Tommaso
Fazio, Leonardo
Angrisano, Tiziana
Iacovelli, Luisa
Porcelli, Annamaria
Maddalena, Giancarlo
Punzi, Giovanna
Mancini, Marina
Gelao, Barbara
Romano, Raffaella
Masellis, Rita
Calabrese, Francesca
Rampino, Antonio
Taurisano, Paolo
Di Giorgio, Annabella
Keller, Simona
Tarantini, Letizia
Sinibaldi, Lorenzo
Quarto, Tiziana
Popolizio, Teresa
Caforio, Grazia
Blasi, Giuseppe
Riva, Marco A.
De Blasi, Antonio
Chiariotti, Lorenzo
Bollati, Valentina
Bertolino, Alessandro

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