Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes

Thymic development produces two sub-lineages of T cells expressing either CD4 or CD8 co-receptors that assist antibody production and mediate cell killing, respectively. The mechanisms for mutually exclusive co-receptor expression remain poorly defined. We find that mutations in the high mobility group (HMG) domain of BAF57--a DNA-binding subunit of the mammalian SWI/SNF-like chromatin-remodelling BAF complexes--or in the BAF complex ATPase subunit Brg, impair both CD4 silencing and CD8 activation. Brg is haploinsufficient for CD8 activation, but not for CD4 silencing, whereas BAF57 mutations preferentially impair CD4 silencing, pointing to target- and subunit-specific mechanisms of chromatin remodelling. BAF complexes directly bind the CD4 silencer, but the BAF57 HMG domain is dispensable for tethering BAF complexes to the CD4 silencer or other chromatin loci in vivo, or for remodelling reconstituted templates in vitro, suggesting that chromatin remodelling in vivo requires HMG-dependent DNA bending. These results indicate that BAF complexes contribute to lineage bifurcation by reciprocally regulating lineage-specific genes, reminiscent of the role of the yeast SWI/SNF complex in mediating mating-type switching.     

Dynamic analysis of DNA damage induced miRNAs in colon cancer cells

It is known that microRNAs （miRNAs） expression profile shows substantial changes in cells under DNA damage. Here, we did miRNA microarray and quantitative real-time PCR to comprehensively identify the differentially expressed miRNAs in colon cancer cell lines HCT116 p53＋/＋ and HCT116 p53-/-. Cluster analysis revealed a panel of differentially expressed miRNAs which are regulated by p53 and/or UV-C induced DNA damage. These altered miRNAs tend to be located in chromosomes 13, X and 17. Moreover, pathways enrichment analysis estimated that MAPK pathway, focal adheren pathway, p53 pathway and Wnt pathway were mediated by these miRNAs to exert their functions in DNA damage response. Additionally, we found that miR- 320a, one of the UV-C induced miRNAs, play a role in protecting cells from DNA damage. Taken together, our results show that miRNAs are dynamic regulated in p53- dependent or -independent manners in different cell contexts and different situations following DNA damage.     

不同运动强度对急性心肌梗死大鼠心功能的影响及循环miRNAs差异表达

研究不同运动强度对急性心肌梗死大鼠心功能的影响, 分析循环微小RNA(microRNAs, miRNAs)的差异表达与靶基因及基因功能. 制作急性心肌梗死大鼠模型40只,分为4组, 每组10只, 分别为假手术组、单纯心肌梗死组、中等强度持续运动(continuous moderate training, CMT)组和间歇高强度运动(high intensity interval training, HIT)组, CMT组和HIT组大鼠接受运动治疗8周, 用超声心动图评估心功能, 用基因芯片技术测定4组大鼠模型循环miRNAs差异表达, 用生物信息学技术分析不同运动强度下循环miRNAs相关靶基因及基因功能. CMT组和HIT组的治疗显著改善了心肌梗死大鼠心功能和运动耐量, HIT组显著优于CMT组. 单纯心肌梗死组与假手术组相比, 明显上调的循环miRNAs有14个, 明显下调的循环miRNAs有4个. 与单纯心肌梗死组相比, CMT组明显上调的循环miRNAs有11个, 明显下调的循环miRNAs有2个; HIT组明显上调的循环miRNAs有53个, 明显下调的关键miRNAs有41个. 与假手术组相比, 单纯心肌梗死组心肌相关循环miRNAs的差异表达有miR-26a-5p, miR-92a-3p和miR-378a-3p; 与单纯心肌梗死组相比, CMT组有miR-92a-3p, HIT组有miR-34c-3p, miR-23a-3p, miR-98-3p, miR-208a-5p和miR-92-3p. 高强度间歇运动对心肌梗死大鼠心功能和运动耐量的改善作用优于中等强度持续运动, 其循环miRNAs及心肌相关循环miRNAs的差异表达数量明显高于中等强度持续运动, 循环miRNAs差异表达有望作为运动强度和运动效果判断的分子生物学标志物.     

CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation

Cytoplasmic polyadenylation-induced translation controls germ cell development, neuronal synaptic plasticity and cellular senescence, a tumour-suppressor mechanism that limits the replicative lifespan of cells. The cytoplasmic polyadenylation element binding protein (CPEB) promotes polyadenylation by nucleating a group of factors including defective in germline development 2 (Gld2), a non-canonical poly(A) polymerase, on specific messenger RNA (mRNA) 3' untranslated regions (UTRs). Because CPEB regulation of p53 mRNA polyadenylation/translation is necessary for cellular senescence in primary human diploid fibroblasts, we surmised that Gld2 would be the enzyme responsible for poly(A) addition. Here we show that depletion of Gld2 surprisingly promotes rather than inhibits p53 mRNA polyadenylation/translation, induces premature senescence and enhances the stability of CPEB mRNA. The CPEB 3' UTR contains two miR-122 binding sites, which when deleted, elevate mRNA translation, as does an antagomir of miR-122. Although miR-122 is thought to be liver specific, it is present in primary fibroblasts and destabilized by Gld2 depletion. Gld4, a second non-canonical poly(A) polymerase, was found to regulate p53 mRNA polyadenylation/translation in a CPEB-dependent manner. Thus, translational regulation of p53 mRNA and cellular senescence is coordinated by Gld2/miR-122/CPEB/Gld4.     

miR-1/133基因簇的进化及其调控网络

miR-1/133基因簇在心肌和骨骼肌中特异性表达,对心脏以及骨骼肌的发育及生理病理具有重要作用.该研究采用生物信息学方法,研究了miR-1/133基因簇的进化特征,预测了其靶基因及其调控的生物学过程.利用miRBase数据库对23种不同物种间miR-1/133基因簇的序列、组织方式进行了比较.采用最大似然法构建miR-1/133基因簇的系统进化树,显示该基因簇的进化与物种进化关系有一定差异.利用在线数据库对miR-1/133基因簇上游转录因子及下游靶基因进行预测,并对其进行综合分析,绘制出该基因簇的网络调控图,表明miR-1/133基因簇参与了骨骼肌与心肌发育、胰岛素受体信号通路、经典Wnt信号通路、p53信号通路等体内重要生理过程,为进一步阐明miR-1/133基因簇的生物学功能提供了理论依据.