Possible involvement of DNA breaks in epigenetic regulation of cell differentiation

The review summarizes the authors’ and literature data on accumulation of DNA breaks in differentiating cells. Large 50-kb free DNA fragments were observed by several research teams in non-apoptotic insect, mammal, and plant cells. More intense DNA breakage was observed during maturation of spermatides, embryo development, and differentiation of myotubes, epidermal cells, lymphocytes, and neutrophils. In general, accumulation of DNA breaks in differentiating cells cannot be attributed to a decrease in the DNA repair efficiency. Poly(ADP)ribose synthesis often follows the DNA breakage in differentiating cells. We hypothesize that DNA fragmentation is an epigenetic tool for regulating the differentiation process. Scarce data on localization of the differentiation-associated DNA breaks indicate their preferable accumulation in specific DNA sequences including the nuclear matrix attachment sites. The same sites are degraded at early stages of apoptosis. Recent data on non-apoptotic function of caspases provide more evidence for possible existence of a DNA breakage mechanism in differentiating cells, resembling the initial stage of apoptosis. Excision of methylated cytosine and recombination are other possible explanations of the phenomenon. Elucidation of mechanisms of differentiation-induced DNA breaks appears to be a prospective research direction.     

Selective diapedesis of Th1 cells induced by endothelial cell RANTES.

Differentiated CD4 T cells can be divided into Th1 and Th2 types based on the cytokines they produce. Differential expression of chemokine receptors on either the Th1-type or the Th2-type cell suggests that Th1-type and Th2-type cells differ not only in cytokine production but also in their migratory capacity. Stimulation of endothelial cells with IFN-gamma selectively enhanced transmigration of Th1-type cells, but not Th2-type cells, in a transendothelial migration assay. Enhanced transmigration of Th1-type cells was dependent on the chemokine RANTES produced by endothelial cells, as indicated by the findings that Ab neutralizing RANTES, or Ab to its receptor CCR5, inhibited transmigration. Neutralizing Ab to chemokines macrophage-inflammatory protein-1alpha or monocyte chemotactic protein-1 did not inhibit Th1 selective migration. Whereas anti-CD18 and anti-CD54 blocked basal levels of Th1-type cell adherence to endothelial cells and also inhibited transmigration, anti-RANTES blocked only transmigration, indicating that RANTES appeared to induce transmigration of adherent T cells. RANTES seemed to promote diapedesis of adherent Th1-type cells by augmenting pseudopod formation in conjunction with actin rearrangement by a pathway that was sensitive to the phosphoinositol 3-kinase inhibitor wortmannin and to the Rho GTP-binding protein inhibitor, epidermal cell differentiation inhibitor. Thus, enhancement of Th1-type selective migration appeared to be responsible for the diapedesis induced by interaction between CCR5 on Th1-type cells and RANTES produced by endothelial cells. Further evidence that CCR5 and RANTES play a modulatory role in Th1-type selective migration derives from the abrogation of this migration by anti-RANTES and anti-CCR5 Abs.     

Ellesmeris sphenopteroides,gen. ET SP. NOV., a new zygopterid fern from the Upper Devonian (Frasnian) of Ellesmere,N.W.T., Arctic Canada

A new fern-like fossil plant is described from the lower Upper Devonian of southern Ellesmere Island, Canadian Arctic Archipelago. The plant occurs in an Archaeopteris-dominated flora preserved in the Nordstrand Point Formation (Mid-Late Frasnian) near Bird Fiord. The plant has a pinnate vegetative system with three branch orders and laminate sphenopteroid pinnules. Primary pinnae usually diverge from the main axis in distichous pairs (quadriseriate), but can depart singly (biseriate). Each primary pinna bears a basal catadromic aphlebia. Anatomically, the plant exhibits a mesarch, bipolar protostele that is ribbon- to clepsydropsoid-shaped in the main axis. Primary pinna traces are also initially bipolar and crescent-shaped, but may become four-ribbed before dividing into a pair of bipolar traces. The morphology and anatomy of this plant are nongymnospermous and are most similar to Zygopteridales (particularly Rhacophytaceae and Zygopteridaceae). The Frasnian age of Ellesmeris shows that laminated foliage had evolved in some zygopterid ferns much earlier than previously recognized. The Sphenopteris-like pinnules of Ellesmeris indicate the need for caution when attributing such a convergent foliar design to other plant groups, such as the Devonian gymnosperms.