Histones modifications and their impact on epigenomics

Histone PTMs, together with DNA methylation and the noncoding RNA (ncRNA), represent an ensemble of epigenetic changes responsible for different states of chromatin arrangement. Histone PTMs can be divided in two main groups. The?rst group comprises PTMs leading to the addition or removal of generally small, organic substituents. The second group of PTMs includes large, organic molecules. Modi?cations of this group are ubiquitylation, SUMOylation, biotinylation, glycosylation (O-GlcNAcylation) and ADP-ribosylation.

Histone PTMs, together with DNA methylation and the noncoding RNA (ncRNA), represent an ensemble of epigenetic changes responsible for different states of chromatin arrangement. Histone PTMs can be divided in two main groups. The?rst group comprises PTMs leading to the addition or removal of generally small, organic substituents. The second group of PTMs includes large, organic molecules. Modi?cations of this group are ubiquitylation, SUMOylation, biotinylation, glycosylation (O-GlcNAcylation) and ADP-ribosylation.

Lysine histone N-methylation is a universal post-translational modification that can signal either for transcriptional repression or activation in a site- and context-specific manner. Its removal is catalyzed by members of either or both of two histone lysine demethylases families. One is the Jumonji C (JmjC) enzymes, which are 2-oxoglutarate (2OG) dependent oxygenases. The other family belongs to the flavin adenine dinucleotide (FAD)-dependent amine oxidase superfamily.

KDM6B and KDM6A regulate transcription in a non-catalytic manner via their interactions with T-box proteins. Down-regulation of UTY is associated with an increased risk of male cardiovascular disease.

Demethylation was assessed by a mass spectrometric assay with mass shifts of -14 and -28 Da, corresponding to mono- and di-demethylation, respectively. We also carried out crystallographic studies on the catalytic domain of UTY and find Uty has a similar 3D structure to KDM6A/B.

UTY acts on substrates other than histones; indeed there is increasing evidence that lysine methylation / demethylation of non-histone proteins, at present to a lesser extent than for histones, play important roles in multiple regulatory pathways. We have provided biochemical evidence that purified UTY can act as a KDM. The study expands the set of human KDMs and will be of use in developing selective KDM inhibitors.

Both obesity and type 2 diabetes have a heritable component that is not completely attributable to genetic variation. There are more and more evidences supporting that epigenetics may play an additional role in mediating inheritance of disease risk. Among early environmental exposures, nutrition plays a key role predisposing to type 2 diabetes, not only to exposed individuals, but also to their offspring and even their grand-offspring.

Here, we have developed a mouse model of intrauterine growth restriction (IUGR) by in utero malnutrition. IUGR impact the expression of lipogenic genes in the second-generation offspring. Lxra and srebf1 contribute to regulate expression of lipogenic genes in IUGR-F2 mice. We test the ideal that deregulated Lxra expression contributed to the development of metabolic dysfunction and found it might, at least in part, be explained by altered epigenetic modi?cations.

Our study indicate that in utero malnutrition results in epigenetic modi?cations in germ cells that are then transmitted and maintained in somatic cells of the F2, thereby in?uencing health and disease risk of the offspring.

Understanding of mechanisms mediating such non-Mendelian forms of inheritance is clearly relevant to design nutritional interventions aimed to prevent such effects and improve health of the upcoming generations.

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.