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- Trends Genet 27(11):i (2011)
- Evidence for Fisher's dominance theory: how many 'special cases'?
- Trends Genet 27(11):441-445 (2011)
Dominance, its genetic basis and evolution has been at the heart of one of the most intense controversies in the history of genetics. For more than eighty years the existence of dominance modifiers, genetic elements controlling dominanceâ"recessivity interactions, has been suggested as a theoretical possibility, but the modifier elements themselves have remained elusive. A recent study of the self-incompatibility locus in flowering plants provided the first empirical evidence for such genetic elements: small non-coding RNAs that control dominanceâ"recessivity by mediating methylation of the promoter of the recessive allele. Theory has shown that several biological situations are favorable for the evolution of dominance modifiers. We argue that the elucidation of this mechanism of dominance opens up new research avenues that could lead to uncovering dominance modifiers in other genetic systems, such as genes controlling Batesian and Müllerian mimicry or host�! �"parasite interactions, thereby shedding light on the generality of the proposed mechanism. - The aneuploidy paradox: costs and benefits of an incorrect karyotype
- Trends Genet 27(11):446-453 (2011)
Aneuploidy has a paradoxical effect on cell proliferation. In all normal cells analyzed to date, aneuploidy has been found to decrease the rate of cell proliferation. Yet, aneuploidy is also a hallmark of cancer, a disease of enhanced proliferative capacity, and aneuploid cells are frequently recovered following the experimental evolution of microorganisms. Thus, in certain contexts, aneuploidy might also have growth-advantageous properties. New models of aneuploidy and chromosomal instability have shed light on the diverse effects that karyotypic imbalances have on cellular phenotypes, and suggest novel ways of understanding the role of aneuploidy in development and disease. - Polycomb group proteins: repression in 3D
- Trends Genet 27(11):454-464 (2011)
Polycomb group (PcG) proteins are well-conserved chromatin factors that repress the transcription of their target genes. They bind to the genome at specific sites and act on chromatin through the regulation of both post-translational histone modifications and higher-order chromatin structure. Recent work has revealed that PcG-bound regulatory regions can interact with promoters and modulate their activity via mechanisms involving looping between regulatory elements and also long-distance interactions in cis or in trans (on different chromosomes). This indicates that the 3D organization of PcG proteins contributes significantly to their function. Moreover, because long-range chromosomal contacts have been shown to involve many genomic loci in addition to Polycomb target genes, their regulatory impact could extend beyond the function of Polycomb proteins. - Pioneer factors: directing transcriptional regulators within the chromatin environment
- Trends Genet 27(11):465-474 (2011)
Chromatin is a well-known obstacle to transcription as it controls DNA accessibility, which directly impacts the recruitment of the transcriptional machinery. The recent burst of functional genomic studies provides new clues as to how transcriptional competency is regulated in this context. In this review, we discuss how these studies have shed light on a specialized subset of transcription factors, defined as pioneer factors, which direct recruitment of downstream transcription factors to establish lineage-specific transcriptional programs. In particular, we present evidence of an interplay between pioneer factors and the epigenome that could be central to this process. Finally, we discuss how pioneer factors, whose expression and function are altered in tumors, are also being considered for their prognostic value and should therefore be regarded as potential therapeutic targets. Thus, pioneer factors emerge as key players that connect the epigenome and transcription ! in health and disease. - Genomic and chromatin signals underlying transcription start-site selection
- Trends Genet 27(11):475-485 (2011)
A central question in cellular biology is how the cell regulates transcription and discerns when and where to initiate it. Locating transcription start sites (TSSs), the signals that specify them, and ultimately elucidating the mechanisms of regulated initiation has therefore been a recurrent theme. In recent years substantial progress has been made towards this goal, spurred by the possibility of applying genome-wide, sequencing-based analysis. We now have a large collection of high-resolution datasets identifying locations of TSSs, proteinâ"DNA interactions, and chromatin features over whole genomes; the field is now faced with the daunting challenge of translating these descriptive maps into quantitative and predictive models describing the underlying biology. We review here the genomic and chromatin features that underlie TSS selection and usage, focusing on the differences between the major classes of core promoters.
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