Zhen Shao

Lactic acid bacteria are a kind of microorganisms that can ferment carbohydrates to produce lactic acid, and are currently widely used in the fermented food industry. In recent years, with the excellent role of lactic acid bacteria in the food industry and probiotic functions, their microbial metabolic characteristics have also attracted more attention. Lactic acid bacteria can decompose macromolecular substances in food, including degradation of indigestible polysaccharides and transformation of undesirable flavor substances. Meanwhile, they can also produce a variety of products including short-chain fatty acids, amines, bacteriocins, vitamins and exopolysaccharides during metabolism. Based on the above-mentioned metabolic characteristics, lactic acid bacteria have shown a variety of expanded applications in the food industry. On the one hand, they are used to improve the flavor of fermented foods, increase the nutrition of foods, reduce harmful substances, increase shelf life, and so on. On the other hand, they can be used as probiotics to promote health in the body. This article reviews and prospects the important metabolites in the expanded application of lactic acid bacteria from the perspective of bioengineering and biotechnology.

Genome-wide association studies (GWASs) have ascertained numerous trait-associated common genetic variants, frequently localized to regulatory DNA. We found that common genetic variation at BCL11A associated with fetal hemoglobin (HbF) level lies in noncoding sequences decorated by an erythroid enhancer chromatin signature. Fine-mapping uncovers a motif-disrupting common variant associated with reduced transcription factor (TF) binding, modestly diminished BCL11A expression, and elevated HbF. The surrounding sequences function in vivo as a developmental stage-specific, lineage-restricted enhancer. Genome engineering reveals the enhancer is required in erythroid but not B-lymphoid cells for BCL11A expression. These findings illustrate how GWASs may expose functional variants of modest impact within causal elements essential for appropriate gene expression. We propose the GWAS-marked BCL11A enhancer represents an attractive target for therapeutic genome engineering for the β-hemoglobinopathies.

ChIP-Seq is widely used to characterize genome-wide binding patterns of transcription factors and other chromatin-associated proteins. Although comparison of ChIP-Seq data sets is critical for understanding cell type-dependent and cell state-specific binding, and thus the study of cell-specific gene regulation, few quantitative approaches have been developed. Here, we present a simple and effective method, MAnorm, for quantitative comparison of ChIP-Seq data sets describing transcription factor binding sites and epigenetic modifications. The quantitative binding differences inferred by MAnorm showed strong correlation with both the changes in expression of target genes and the binding of cell type-specific regulators.

Persistence of human fetal hemoglobin (HbF, α(2)γ(2)) in adults lessens the severity of sickle cell disease (SCD) and the β-thalassemias. Here, we show that the repressor BCL11A is required in vivo for silencing of γ-globin expression in adult animals, yet dispensable for red cell production. BCL11A serves as a barrier to HbF reactivation by known HbF inducing agents. In a proof-of-principle test of BCL11A as a potential therapeutic target, we demonstrate that inactivation of BCL11A in SCD transgenic mice corrects the hematologic and pathologic defects associated with SCD through high-level pancellular HbF induction. Thus, interference with HbF silencing by manipulation of a single target protein is sufficient to reverse SCD.