Histone H3 lysine 4 trimethylation (H3K4me3) is well known to occur in the promoter region of genes for transcription activation.However,when investigating the H3K4me3 profiles in the mouse cerebrum and testis,we discovered that H3K4me3 also has a significant enrichment at the 3' end of actively transcribed (sense) genes,named as 3′-H3K4me3.3′-H3K4me3 is associated with ～15％ of protein-coding genes in both tissues.In addition,we examined the transcriptional initiation signals including RNA polymerase II (RNAPII)binding sites and 5′-CAGE-tag that marks transcriptional start sites.Interestingly,we found that 3′-H3K4me3 is associated with the initiation of antisense transcription.Furthermore,3′-H3K4me3 modification levels correlate positively with the antisense expression levels of the associated sense genes,implying that 3′-H3K4me3 is involved in the activation of antisense transcription.Taken together,our findings suggest that H3K4me3 may be involved in the regulation of antisense transcription that initiates from the 3′ end of sense genes.In addition,a positive correlation was also observed between the expression of antisense and the associated sense genes with 3'-H3K4me3 modification.More importantly,we observed the 3'-H3K4me3 enrichment among genes in human,fruitfly and Arabidopsis,and found that the sequences of 3'-H3K4me3-marked regions are highly conserved and essentially indistinguishable from known promoters in vertebrate.Therefore,we speculate that these 3'-H3K4me3-marked regions may serve as potential promoters for antisense transcription and 3′-H3K4me3 appear to be a universal epigenetic feature in eukaryotes.Our results provide a novel insight into the epigenetic roles of H3K4me3 and the regulatory mechanism of antisense transcription.

Objective:Elderly patients with sarcopenia and cognitive impairment are prone to experiencing more severe adverse events.This study aimed to analyze body composition and gait characteristics in this population, as well as to identify sensitive gait indicators of sarcopenia in individuals with cognitive impairment.Methods:A total of 200 elderly individuals from 3 different nursing homes in Suzhou were recruited for this study.The participants' overall cognitive function was assessed using the Beijing version of the Montreal Cognitive Assessment(MoCA-BJ), body composition was evaluated through bioelectrical impedance analysis, and gait was assessed using a wearable gait analysis system.Gait predictors of sarcopenia with cognitive impairment were then identified and used to construct predictive models.Results:The study encompassed 83 participants, divided into three groups: 35 in the control group(cognitively normal, without sarcopenia), 24 in the sarcopenia with mild cognitive impairment(MCI)group, and 24 in the sarcopenia with dementia group.When compared to the control group, individuals in the sarcopenia with MCI group exhibited lower Skeletal Muscle Mass Index[(5.6±0.8)kg/m 2vs.(7.4±0.8)kg/m 2], Total Protein[(6.7±1.1)kg vs.(8.9±1.5)kg], and Arm Muscle Circumference[(21.4±1.7)cm vs.(24.1±2.3)cm](all P<0.05).Similarly, in comparison to the control group, those in the sarcopenia with dementia group displayed a shorter stride length[(0.45±0.17)m vs.(0.65±0.22)m], slower gait speed[(0.38±0.13)m/s vs.(0.55±0.18)m/s], smaller turn velocity[(89.8±23.4)degrees/s vs.(116.8±26.3)degrees/s], and longer turn duration[(3.2±0.5)s vs.(2.8±0.3)s](all P<0.05).Notably, turn duration was identified as having predictive value for sarcopenia with MCI[Area under the curve(AUC)=0.673, sensitivity 70.8%, specificity 68.6%], while a model incorporating age and turn velocity demonstrated strong predictive power for sarcopenia with dementia(AUC=0.87, sensitivity 83.3%, specificity 85.7%). Conclusions:Compared to the control group, the group with both sarcopenia and cognitive impairment exhibited lower levels of muscle strength, nutritional status, and gait performance.This study also introduced the concept that gait indicators associated with turns could be a significant predictor of sarcopenia in individuals with cognitive impairment.Furthermore, the use of wearable devices for gait assessment may offer a novel approach to identifying these at-risk individuals.

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,wegenerated the genome-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChlP-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.