Investigation of measurable residual disease in acute myeloid leukemia by DNA methylation patterns.

Assessment of measurable residual disease (MRD) upon treatment of acute myeloid leukemia (AML) remains challenging. It is usually addressed by highly sensitive PCR- or sequencing-based screening of specific mutations, or by multiparametric flow cytometry. However, not all patients have suitable mutations and heterogeneity of surface markers hampers standardization in clinical routine.

Zinc deficiency leads to reduced interleukin-2 production by active gene silencing due to enhanced CREMα expression in T cells.

Background & Aims: The micronutrient zinc is essential for proper immune function. Consequently, zinc deficiency leads to impaired immune function, as seen in decreased secretion of interleukin (IL)-2 by T cells. Although this association has been known since the late 1980s, the underlying molecular mechanisms are still unknown.

New targeted approaches for epigenetic age predictions.

Background: Age-associated DNA methylation changes provide a promising biomarker for the aging process. While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurements at specific CpGs that better support standardized and cost-effective high-throughput analysis.

Results: In this study, we utilized 4647 Illumina BeadChip profiles of blood to select CpG sites that facilitate reliable age-predictions based on pyrosequencing.

Genetic barcoding reveals clonal dominance in iPSC-derived mesenchymal stromal cells.

Background: The use of mesenchymal stromal cells (MSCs) for research and clinical application is hampered by cellular heterogeneity and replicative senescence. Generation of MSC-like cells from induced pluripotent stem cells (iPSCs) may circumvent these limitations, and such iPSC-derived MSCs (iMSCs) are already tested in clinical trials. So far, a comparison of MSCs and iMSCs was particularly addressed in bulk culture.

Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging.

Background: There is a growing interest in simple molecular biomarkers for biological aging. Age-associated DNA methylation (DNAm) changes at specific CG dinucleotides can be combined into epigenetic age predictors to estimate chronological age-and the deviation of chronological and predicted age (∆) seems to be associated with all-cause mortality. In this study, we have further validated this association and analyzed whether or not individual age-associated CG-dinucleotides (CpGs) are related to life expectancy.

Allium telomeres unmasked: the unusual telomeric sequence (CTCGGTTATGGG)n is synthesized by telomerase.

Phylogenetic divergence in Asparagales plants is associated with switches in telomere sequences. The last switch occurred with divergence of the genus Allium (Amaryllidaceae) from the other Allioideae (formerly Alliaceae) genera, resulting in uncharacterized telomeres maintained by an unknown mechanism. To characterize the unknown Allium telomeres, we applied a combination of bioinformatic processing of transcriptomic and genomic data with standard approaches in telomere biology such as BAL31 sensitivity tests, terminal restriction fragment analysis, the telomere repeat amplification protocol (TRAP), and fluorescence in situ hybridization (FISH).

Telomere binding protein TRB1 is associated with promoters of translation machinery genes in vivo.

Recently we characterised TRB1, a protein from a single-myb-histone family, as a structural and functional component of telomeres in Arabidopsis thaliana. TRB proteins, besides their ability to bind specifically to telomeric DNA using their N-terminally positioned myb-like domain of the same type as in human shelterin proteins TRF1 or TRF2, also possess a histone-like domain which is involved in protein-protein interactions e.g.

Characterisation of an unusual telomere motif (TTTTTTAGGG)n in the plant Cestrum elegans (Solanaceae), a species with a large genome.

The characterization of unusual telomere sequence sheds light on patterns of telomere evolution, maintenance and function. Plant species from the closely related genera Cestrum, Vestia and Sessea (family Solanaceae) lack known plant telomeric sequences. Here we characterize the telomere of Cestrum elegans, work that was a challenge because of its large genome size and few chromosomes (1C 9.

Nucleosomal TATA-switch: competing orientations of TATA on the nucleosome.

Transcription is known to be affected by the rotational setting of the transcription response elements within nucleosomes. We studied the rotational positioning of the TATA box, the most universal promoter motif. We applied a bioinformatic high-resolution nucleosome mapping technique to eukaryotic promoters.

High resolution positioning of intron ends on the nucleosomes.

High resolution sequence-directed nucleosome mapping is applied to 36,000 sequences containing splice junctions, from five different species. As it has been also shown in previous studies, the junctions are found to be preferentially located within nucleosomes. Moreover, the orientation of guanine residues at the GT- and AG-ends of introns within the nucleosomes is such that the guanines are positioned nearest to the surface of histone octamers, 3 and 4 bases upstream from the local DNA pseudo-dyads passing through minor grooves oriented outwards.