CBP and P300 regulate distinct gene networks required for human primary myoblast differentiation and muscle integrity.

The acetyltransferases CBP and P300 have been implicated in myogenesis in mouse immortalized cell lines but these studies focused only on the expression of a handful of myogenic factors. Hence, the respective role of these two related cofactors and their impact at global scale on gene expression rewiring during primary myoblast differentiation remain unknown. Here, we characterised the gene networks regulated by these two epigenetic enzymes during human primary myoblast differentiation (HPM). We found that CBP and p300 play a critical role in the activation of the myogenic program and mostly regulate distinct gene sets to control several aspects of HPM biology, even though they also exhibit some degree of redundancy. Moreover, CBP or P300 knockdown strongly impaired muscle cell adhesion and resulted in the activation of inflammation markers, two hallmarks of dystrophic disease. This was further validated in zebrafish where inhibition of CBP and P300 enzymatic activities led to cell adhesion defects and muscle fiber detachment. Our data highlight an unforeseen link between CBP/P300 activity and the emergence of dystrophic phenotypes. They thereby identify CBP and P300 as mediators of adult muscle integrity and suggest a new lead for intervention in muscular dystrophy.

Multiple micronutrient deficiencies persist during early childhood in Mongolia.

Data on the prevalence of micronutrient deficiencies in children in Mongolia is limited. We therefore determined the prevalence of anaemia, iron deficiency anaemia (IDA), and deficiencies of iron, folate, vitamin A, zinc, selenium, and vitamin D among young Mongolian children. Anthropometry and non-fasting morning blood samples were collected from 243 children aged 6-36 months from 4 districts in Ulaanbaatar and 4 rural capitols for haemoglobin (Hb), serum ferritin, folate, retinol, zinc, selenium, and 25-hydroxyvitamin D (25-OHD) assays. Children with alpha-1-glycoprotein >1.2mg/L (n=27) indicative of chronic infection were excluded, except for folate, selenium, and 25-hydroxyvitamin D assays. Of the children 14.5% were stunted and none were wasted. Zn deficiency (serum Zn <9.9 micromol/L) had the highest prevalence (74%), followed by vitamin D deficiency 61% (serum 25-OHD<25 nmol/L). The prevalence of anaemia (24%) and iron deficiency anaemia (IDA) (16%) was lower, with the oldest children (24-36 mos) at lowest risk. Twenty one percent of the children had low iron stores, and 33% had vitamin A deficiencies (serum retinol < 0.70 micromol/L), even though two thirds had received vitamin A supplements. Serum selenium values were low, perhaps associated with low soil selenium concentrations. In contrast, no children in Ulaanbaatar and only 4% in the provincial capitols had low serum folate values (<6.8 nmol/L). Regional differences (p<0.05) existed for anaemia, deficiencies of vitamin A, folate, and selenium, but not for zinc or IDA. Of the children, 78% were at risk of > or = two coexisting micronutrient deficiencies emphasizing the need for multimicronutrient interventions in Mongolia.