Sequence-specific recognition of methylated DNA by human zinc-finger proteins

DNA methylation is an essential epigenetic mark. Three classes of mammalian proteins recognize methylated DNA: MBD proteins, SRA proteins and the zinc-finger proteins Kaiso, ZBTB4 and ZBTB38. The last three proteins can bind either methylated DNA or unmethylated consensus sequences; how this is achieved is largely unclear. Here, we report that the human zinc-finger proteins Kaiso, ZBTB4 and ZBTB38 can bind methylated DNA in a sequence-specific manner, and that they may use a mode of binding common to other zinc-finger proteins. This suggests that many other sequence-specific methyl binding proteins may exist.     

Direct-to-consumer genetic testing through Internet: marketing, ethical and social issues

We probably did not anticipate all the consequences of the direct to consumer genetic tests on Internet, resulting from the combined skills of communication and genomic advances. What are the commercial strategies used by the companies offering direct-to-consumer genetic tests on Internet and what are the different social expectations on which they focus? Through a quantitative and qualitative analysis of the web sites offering such tests, it seems that these companies target a triple market based on: the "healthism" which raises health and hygiene to the top of the social values; the contemporary demands of the users to become actual actors of health decisions; and finally on the need for bio-social relationships. These three commercial strategies underlie various ethical and societal issues justifying a general analysis.     

The cell biology of DNA methylation in mammals

In this review, we will provide a brief reminder of epigenetic phenomena in general, and DNA methylation in particular. We will then underline the characteristics of the in vivo organization of the genome that limit the applicability of in vitro results. We will use several examples to point out the connections between DNA methylation and nuclear architecture. Finally, we will outline some of the hopes and challenges for future research in the field. The study of DNA methylation, its effectors, and its roles, illustrates the complementarity of in vitro approaches and cell biology.     

Alpha Satellite Insertion Close to an Ancestral Centromeric Region

Human centromeres are mainly composed of alpha satellite DNA hierarchically organized as higher-order repeats (HORs). Alpha satellite dynamics is shown by sequence homogenization in centromeric arrays and by its transfer to other centromeric locations, for example, during the maturation of new centromeres. We identified during prenatal aneuploidy diagnosis by fluorescent in situ hybridization a de novo insertion of alpha satellite DNA from the centromere of chromosome 18 (D18Z1) into cytoband 15q26. Although bound by CENP-B, this locus did not acquire centromeric functionality as demonstrated by the lack of constriction and the absence of CENP-A binding. The insertion was associated with a 2.8-kbp deletion and likely occurred in the paternal germline. The site was enriched in long terminal repeats and located ∼10 Mbp from the location where a centromere was ancestrally seeded and became inactive in the common ancestor of humans and apes 20–25 million years ago. Long-read mapping to the T2T-CHM13 human genome assembly revealed that the insertion derives from a specific region of chromosome 18 centromeric 12-mer HOR array in which the monomer size follows a regular pattern. The rearrangement did not directly disrupt any gene or predicted regulatory element and did not alter the methylation status of the surrounding region, consistent with the absence of phenotypic consequences in the carrier. This case demonstrates a likely rare but new class of structural variation that we name “alpha satellite insertion.” It also expands our knowledge on alphoid DNA dynamics and conveys the possibility that alphoid arrays can relocate near vestigial centromeric sites.     

Master and servant: epigenetic deregulations as a cause and a consequence of cancer

The processes that affect the activity of the genome in a heritable manner without changing its sequence are called epigenetic. Here we review the modes of epigenetic gene regulation, and describe their alterations in cancer. We show how these mechanisms are interdependent, and how they intersect with genetic mutations. We argue that epigenetic abnormalities can occur both as a cause, and as a consequence of cancer. Indeed, oncogenic transformation can deeply alter the epigenetic information contained in the pattern of DNA methylation or histone tail modification. Conversely, epigenetic dysfunctions can drive cellular transformation. We then touch on some practical consequences of the prominence of epigenetic alterations in cancer : increasing knowledge of this field has allowed the development of a new generation of diagnostic tools and therapeutic avenues. Finally we point out that epigenetic phenomena may act as sensors that link environmental conditions to cancer.