Fasting alters histone methylation in paraventricular nucleus through regulating of polycomb repressive complex 2

摘要: The developing brain is highly sensitive to environmental influences. Unfavorable nutrition one kind of stress that can cause acute metabolic disorders during the neonatal period [1,2,3] and severe diseases in later life [4,5]. These early experiences occurring heightened periods plasticity help determine lifelong structural functional aspects behavior. In humans, for example, weight gain first week increased propensity obesity several decades [5]. This susceptibility is, if not all, related dynamic reversible epigenetic imprints left on histones [6,7,8], especially prenatal postpartum [9]. Histones are responsive towards [10,11]. Through covalent modification histone tail, able direct DNA scaffolding regulate gene expression [10,12]. Thus far, various types post translational modifications have been identified tails [12]. Among them, methylation acetylation lysine residue (K) 27 3 (H3) has tightly linked repression [13,14] activation [15], respectively. EZh2 (enhancer zeste 2) polycomb repressive complex 2 (PRC2) only methyltransferase catalyze this reaction. addition, SUZ (suppressor zeste) EED (embryonic ectoderm development) two other key proteins PRC2 function core EZH2. As previous reported, H3K27 was monitored after fasting chicks' paraventricular nucleus (PVN). study, we investigated detailed mechanism behind changes following stress. After 24 hours days-of-age (D3), chicks exhibited elevated mRNA levels components, including EZH2, EED, PVN D4. Western blots confirmed finding by showing global status at site until 38 days fasting, EZH2 remained inhibited. A newly anorexigenic factor, Brain-derived neurotrophic factor (BDNF), used as an example multiple hormones expressed verify finding. Both BDNF protein compatible tri(me3) di-methylated (me2) H327. Furthermore, using chromatin immunoprecipitation assays (ChIP), were monitor H3K27me2/me3 deposition along Bdnf gene. Fasting significantly well Bdnf’s promoter, transcription start 3'-untranslated region. data show could leave imprinting a long time. Next, tried understand PVN. Thus, compared naive (never fasted) received either single hour fast D3 or both 10 (D10). We found