bims-meprid Biomed News
on Metabolic-dependent epigenetic reprogramming in differentiation and disease
Issue of 2020‒09‒27
two papers selected by
Alessandro Carrer
Veneto Institute of Molecular Medicine

  1. Cell Prolif. 2020 Sep 26. e12898
      For multicellular organisms, it is essential to produce a variety of specialized cells to perform a dazzling panoply of functions. Chromatin plays a vital role in determining cellular identities, and it dynamically regulates gene expression in response to changing nutrient metabolism and environmental conditions. Intermediates produced by cellular metabolic pathways are used as cofactors or substrates for chromatin modification. Drug analogues of metabolites that regulate chromatin-modifying enzyme reactions can also regulate cell fate by adjusting chromatin organization. In recent years, there have been many studies about how chromatin-modifying drug molecules or metabolites can interact with chromatin to regulate cell fate. In this review, we systematically discuss how DNA and histone-modifying molecules alter cell fate by regulating chromatin conformation and propose a mechanistic model that explains the process of cell fate transitions in a concise and qualitative manner.
    Keywords:  DNA; acetylation; chromatin; histone; metabolism; methylation
  2. Nat Metab. 2020 Sep 21.
      Current immunotherapies yield remarkable clinical outcomes by boosting the power of host immunity in cancer cell elimination and viral clearance. However, after prolonged antigen exposure, CD8+ T cells differentiate into a special differentiation state known as T-cell exhaustion, which poses one of the major hurdles to antiviral and antitumor immunity during chronic viral infection and tumour development. Growing evidence indicates that exhausted T cells undergo metabolic insufficiency with altered signalling cascades and epigenetic landscapes, which dampen effector immunity and cause poor responsiveness to immune-checkpoint-blockade therapies. How metabolic stress affects T-cell exhaustion remains unclear; therefore, in this Review, we summarize current knowledge of how T-cell exhaustion occurs, and discuss how metabolic insufficiency and prolonged stress responses may affect signalling cascades and epigenetic reprogramming, thus locking T cells into an exhausted state via specialized differentiation programming.