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1.  Epigenetic hereditary transcription profiles III, evidence for an epigenetic network resulting in gender, tissue and age-specific variation in overall transcription 
Biology Direct  2009;4:37.
We have previously shown that deviations from the average transcription profile of a group of functionally related genes are not only heritable, but also demonstrate specific patterns associated with age, gender and differentiation, thereby implicating genome-wide nuclear programming as the cause. To determine whether these results could be reproduced, a different micro-array database (obtained from two types of muscle tissue, derived from 81 human donors aged between 16 to 89 years) was studied.
This new database also revealed the existence of age, gender and tissue-specific features in a small group of functionally related genes. In order to further analyze this phenomenon, a method was developed for quantifying the contribution of different factors to the variability in gene expression, and for generating a database limited to residual values reflecting constitutional differences between individuals. These constitutional differences, presumably epigenetic in origin, contribute to about 50% of the observed residual variance which is connected with a network of interrelated changes in gene expression with some genes displaying a decrease or increase in residual variation with age.
Epigenetic variation in gene expression without a clear concomitant relation to gene function appears to be a widespread phenomenon. This variation is connected with interactions between genes, is gender and tissue specific and is related to cellular aging.
This finding, together with the method developed for analysis, might contribute to the elucidation of the role of nuclear programming in differentiation, aging and carcinogenesis
This article was reviewed by Thiago M. Venancio (nominated by Aravind Iyer), Hua Li (nominated by Arcady Mushegian) and Arcady Mushegian and Magelhaes (nominated by G. Church).
PMCID: PMC2762993  PMID: 19796384
2.  Epigenetic hereditary transcription profiles II, aging revisited 
Biology Direct  2007;2:39.
Previously, we have shown that deviations from the average transcription profile of a group of functionally related genes can be epigenetically transmitted to daughter cells, thereby implicating nuclear programming as the cause. As a first step in further characterizing this phenomenon it was necessary to determine to what extent such deviations occur in non-tumorigenic tissues derived from normal individuals. To this end, a microarray database derived from 90 human donors aged between 22 to 87 years was used to study deviations from the average transcription profile of the proteasome genes.
Increase in donor age was found to correlate with a decrease in deviations from the general transcription profile with this decline being gender-specific. The age-related index declined at a faster rate for males although it started from a higher level. Additionally, transcription profiles from similar tissues were more alike than those from different tissues, indicating that deviations arise during differentiation.
These findings suggest that aging and differentiation are related to epigenetic changes that alter the transcription profile of proteasomal genes. Since alterations in the structure and function of the proteasome are unlikely, such changes appear to occur without concomitant change in gene function.
These findings, if confirmed, may have a significant impact on our understanding of the aging process.
Open peer review
This article was reviewed by Nathan Bowen (nominated by I. King Jordan), Timothy E. Reddy (nominated by Charles DeLisi) and by Martijn Huynen. For the full reviews, please go to the Reviewers'comments section.
PMCID: PMC2265679  PMID: 18163906
3.  Hereditary profiles of disorderly transcription? 
Biology Direct  2006;1:9.
Microscopic examination of living cells often reveals that cells from some cell strains appear to be in a permanent state of disarray without obvious reason. In all probability such a disorderly state affects cell functioning.
The aim of this study was to establish whether a disorderly state could occur that adversely affects gene expression profiles and whether such a state might have biomedical consequences. To this end, the expression profiles of the 14 genes of the proteasome derived from the GEO SAGE database were utilized as a model system.
By adopting the overall expression profile as the standard for normal expression, deviation in transcription was frequently observed. Each deviating tissue exhibited its own characteristic profile of over-expressed and under-expressed genes. Moreover such a specific deviating profile appeared to be epigenetic in origin and could be stably transmitted to a clonal derivative e.g. from a precancerous normal tissue to its tumor. A significantly greater degree of deviation was observed in the expression profiles from the tumor tissues.
The changes in the expression of different genes display a network of interdependencies. Therefore our hypothesis is that deviating profiles reflect disorder in the localization of genes within the nucleus
The underlying cause(s) for these disorderly states remain obscure; it could be noise and/or deterministic chaos. Presence of mutational damage does not appear to be predominantly involved.
As disturbances in expression profiles frequently occur and have biomedical consequences, its determination could prove of value in several fields of biomedical research.
This article was reviewed by Trey Ideker, Itai Yanai and Stephan Beck
PMCID: PMC1500996  PMID: 16579860

Results 1-3 (3)