The global features of H3K4 and H3K27 trimethylations(H3K4me3 and H3K27me3) have been well studied in recent years,but most of these studies were performed in mammalian cell lines.In this work,we generated the genome-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChIP-seq and their high-coverage transcriptomes using ribominus RNA-seq with SOLiD technology.We examined the global patterns of H3K4me3 and H3K27me3 in both tissues and found that modifications are closely-associated with tissue-specific expression,function and development.Moreover,we revealed that H3K4me3 and H3K27me3 rarely occur in silent genes,which contradicts the findings in previous studies.Finally,we observed that bivalent domains,with both H3K4me3 and H3K27me3,existed ubiquitously in both tissues and demonstrated an invariable preference for the regulation of developmentally-related genes.However,the bivalent domains tend towards a "winner-takes-all" approach to regulate the expression of associated genes.We also verified the above results in mouse ES cells.As expected,the results in ES cells are consistent with those in cerebrum and testis.In conclusion,we present two very important findings.One is that H3K4me3 and H3K27me3 rarely occur in silent genes.The other is that bivalent domains may adopt a "winner-takes-all" principle to regulate gene expression.
The pluripotent state between human and mouse embryonic stem cells is different.Pluripotent state of human embryonic stem cells(ESCs)is believed to be primed and is similar with that of mouse epiblast stem cells(EpiSCs),which is different from the naïve state of mouse ESCs.Human ESCs could be converted into a naïve state through exogenous expression of defined transcription factors(Hanna et al.,2010).Here we report a rapid conversion of human ESCs to mouse ESC-like naïve states only by modifying the culture conditions.These converted human ESCs,which we called mhESCs(mouse ESC-like human ESCs),have normal karyotype,allow single cell passage,exhibit domed morphology like mouse ESCs and express some pluripotent markers similar with mouse ESCs.Thus the rapid conversion established a naïve pluripotency in human ESCs like mouse ESCs,and provided a new model to study the regulation of pluripotency.
Cyclotides constitute a fascinating family of circular proteins containing ca.30 amino acid residues.They have a unique cyclic cysteine knot topology and exhibit remarkable thermal,chemical and enzymatic stabilities.These characteristics enable them to have a range of biological activities and promising pharmaceutical and agricultural applications.Here,we present a practical strategy for the chemical synthesis of cyclotides through the intramolecular ligation of fully unprotected peptide O-esters.This strategy involves the mild Fmoc solid-phase peptide synthesis of the peptide O-ester backbone,the head-to-tail cyclization of the cyclotide backbone by native chemical ligation,and the oxidative refolding to yield the natural knot protein.The simplicity and high efficiency of the strategy can be employed in the synthesis of artificial cyclotides for pharmaceutical applications.
In the past decade,transition-metal-catalyzed C–H functionalization by weak coordination has emerged as a practical and powerful tool to access many valuable chemicals.Two classes of weakly coordinating directing groups,commonly occurring functional groups,and easily removable auxiliaries,have been found to be efficient and practical for C–H activation reactions.This mini-review contains examples of recent research advances on transition-metal-catalyzed SP2 C–H functionalization via weak coordination,using Ru,Rh,and Pd.A number of weakly coordinating functional groups(e.g.,ketone,ester,carbamate,tertiary amide,ether,thioether,alcohol,and some others)are covered.As the field of transition-metal-catalyzed C–H functionalization continues to develop and more synthetically useful chemo-,regio-,and enantioselective reactions catalyzed by transition metal via weak coordination are discovered,this promising and attractive strategy will play a more important role in modern organic synthesis.
