Functional Epigenetic Regulation in Metabolic Diseases

Metabolic-related gene dysfunction and activation are tightly associated with transcription factor (TF) preference and epigenetic regulations including histone modifications, DNA and RNA methylation, non-coding regulatory RNAs， chromatin conformation, etc. Multiple transcriptional machinery complexes including corepressors, coactivators, TFs, and epigenetic systems are involved in the gene expression regulation both physiologically and pathologically. Any protein depletion or overexpression in this process can cause the downstream gene activation/inactivation via chromatin remodeling and reflect the epigenetic outcomes. As a result, targeting the chromatin remodeling checkpoints is becoming the key to reverse metabolic syndrome and is valuable for translational and precision medicine. Despite this recognition, the current knowledge about how the transcriptional complexes assemble cis- or trans- elements into the promoter region is largely delayed due to the different epigenetic profiles from tissues. The interplaying networks between different factors/cofactors and uncovering the key proteins for chromatin remodeling in gene activation remain to be clarified. It is also important to know the key necessary elements (enhancer) and redundant elements (silencer) from the scientific aspects. To date, the functional epigenetic regulation for metabolic gene activation is still not clear enough.



Future efforts are required to both clinical and animal-based studies to reveal the chromatin remodeling drives gene dysfunction in metabolic syndrome, which includes but are not limited to :

1) DNA accessibility changes (close or open) in specific cell type or tissue which reflects the gene expression;

2) Significant changes of epigenome via histone modifications, cofactor and TFs recruitments under metabolic syndrome (Hyperlipidemia, Inflammation, Fibrosis, etc.);

3) Functional validation via specific element knockout and dCas9-mediated activation/repression;

4) Chromatin conformation to visualize the local DNA interaction contact with the gene promoter； Aberrant DNA and RNA methylation involved in metabolic diseases； Abnormal regulation of endogenous retroviral elements in the human genome.



This research topic aims to summarize current knowledge and to report new findings in epigenetic regulation with a focus on metabolic diseases. Both research articles and reviews are accepted for this topic.