Genome-wide DNA methylation landscape of four Chinese populations and epigenetic variation linked to Tibetan high-altitude adaptation

DNA methylation(DNAm)is one of the major epigenetic mechanisms in humans and is important in diverse cellular processes.The variation of DNAm in the human population is related to both genetic and environmental factors.However,the DNAm profiles have not been investigated in the Chinese population of diverse ethnicities.Here,we performed double-strand bisulfite sequencing(DSBS)for 32 Chinese individuals representing four major ethnic groups including Han Chinese,Tibetan,Zhuang,and Mongolian.We identified a total of 604,649 SNPs and quantified DNAm at more than 14 million Cp Gs in the population.We found global DNAm-based epigenetic structure is different from the genetic structure of the population,and ethnic difference only partially explains the variation of DNAm.Surprisingly,non-ethnic-specific DNAm variations showed stronger correlation with the global genetic divergence than these ethnic-specific DNAm.Differentially methylated regions(DMRs)among these ethnic groups were found around genes in diverse biological processes.Especially,these DMR-genes between Tibetan and nonTibetans were enriched around high-altitude genes including EPAS1 and EGLN1,suggesting DNAm alteration plays an important role in high-altitude adaptation.Our results provide the first batch of epigenetic maps for Chinese populations and the first evidence of the association of epigenetic changes with Tibetans'high-altitude adaptation.

Restricted Feeding Resets Endogenous Circadian Rhythm in Female Mice Under Constant Darkness

Dear Editor,Circadian rhythms are driven by a complex,profoundly integrated network of clocks that maintain physiology and behaviors occurring at precise times and in the right order[1-3].Light,the most powerful zeitgeber,entrains the central clock in the suprachiasmatic nucleus(SCN)via the retinohypothalamic tract with a precise 24-h rhythm in mammals[4,5].Due to irregular exposure to light conditions,such as an arrhythmic lifestyle,jet lag,and shift-work,circadian disturbance occurs quite often in modem societies and promotes a series of health problems such as obesity,depression,and neurodegenerative diseases[6,7].Thus,adjusting or resetting an arrhythmic circadian rhythm by using external cues has attracted wide attention[8].Notably,food-induced cues have been documented to have effects on certain circadian rhythms in rodents and humans[9,10].In nocturnal rodents,time-restricted feeding during the light phase can produce a rhythmic behavior prior to mealtime.

MBRidge: an accurate and cost-effective method for profiling DNA methylome at single-base resolution

Organisms and cells,in response to environmental influences or during development,undergo considerable changes in DNA methylation on a genome-wide scale,which are linked to a variety of biological processes.Using MethylC-seq to decipher DNA methylome at single-base resolution is prohibitively costly.In this study,we develop a novel approach,named MBRidge,to detect the methylation levels of repertoire CpGs,by innovatively introducing C-hydroxylmethylated adapters and bisulfate treatment into the MeDIP-seq protocol and employing ridge regression in data analysis.A systematic evaluation of DNA methylome in a human ovarian cell line T29 showed that MBRidge achieved high correlation(R>0.90)with much less cost(∼10%)in comparison with MethylC-seq.We further applied MBRidge to profiling DNA methylome in T29H,an oncogenic counterpart of T29’s.By comparing methylomes of T29H and T29,we identified 131790 differential methylation regions(DMRs),which are mainly enriched in carcinogenesis-related pathways.These are substantially different from7567 DMRs that were obtained by RRBS and related with cell development or differentiation.The integrated analysis ofDMRsin the promoterand expression of DMR-corresponding genes revealed thatDNAmethylation enforced reverse regulation of gene expression,depending on the distance fromthe proximalDMRto transcription starting sites in both mRNA and lncRNA.Taken together,our results demonstrate that MBRidge is an efficient and cost-effective method that can be widely applied to profiling DNA methylomes.