Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation.

DNA methylation is a fundamental epigenetic modification regulating gene expression. Aberrant DNA methylation is the most common molecular lesion in cancer cells. However, medical intervention has been limited to the use of broadly acting, small molecule-based demethylating drugs with significant side-effects and toxicities.

NAD Modulates DNA Methylation and Cell Differentiation.

Nutritional intake impacts the human epigenome by directing epigenetic pathways in normal cell development via as yet unknown molecular mechanisms. Consequently, imbalance in the nutritional intake is able to dysregulate the epigenetic profile and drive cells towards malignant transformation. Here we present a novel epigenetic effect of the essential nutrient, NAD.

HOXB8 Counteracts MAPK/ERK Oncogenic Signaling in a Chicken Embryo Model of Neoplasia.

HOX transcription factors are members of an evolutionarily conserved family of proteins required for the establishment of the anteroposterior body axis during bilaterian development. Although they are often deregulated in cancers, the molecular mechanisms by which they act as oncogenes or tumor suppressor genes are only partially understood. Since the MAPK/ERK signaling pathway is deregulated in most cancers, we aimed at apprehending if and how the Hox proteins interact with ERK oncogenicity.

HoxB genes regulate neuronal delamination in the trunk neural tube by controlling the expression of .

Differential Hox gene expression is central for specification of axial neuronal diversity in the spinal cord. Here, we uncover an additional function of Hox proteins in the developing spinal cord, restricted to B cluster Hox genes. We found that members of the HoxB cluster are expressed in the trunk neural tube of chicken embryo earlier than Hox from the other clusters, with poor antero-posterior axial specificity and with overlapping expression in the intermediate zone (IZ).

Fattening the perspective of Hox protein specificity through SLiMming.

The functional identification and dissection of protein domains has been a successful approach towards the understanding of Hox protein specificity. However, only a few functional protein domains have been identified; this has been a major limitation in deciphering the molecular modalities of Hox protein action. We explore here, by in silico survey of short linear motifs (SLiMs) in Hox proteins, the contribution of SLiMs to Hox proteins, focusing on the mouse, chick and Drosophila Hox complement.