Objective:Studies have shown thatβ-globin gene presents a selective expression transformation mechanism during development,and its upstream locus control region(LCR)regulates the expression pattern ofβ-globin gene f...Objective:Studies have shown thatβ-globin gene presents a selective expression transformation mechanism during development,and its upstream locus control region(LCR)regulates the expression pattern ofβ-globin gene family.To further explore the molecular network ofβ-globin gene expression regulation,other long-range regulatory elements that may be involved in the regulation ofβ-globin gene expression were screened and the dynamic regulation and transformation mechanism ofβ-globin gene was deeply studied.Methods:Promyelocytic cells were induced to differentiate by all-trans retinoic acid.β-globin gene promoter region and LCR were used as the target sites for circular chromosome conformational capture(4C)analysis.Through sequencing and regulatory element analysis,the sites interacting withβ-globin family loci were screened in the whole genome.Results:According to the results of 4C sequencing,the sites that interact with HBD promoter region and LCR were screened.Verified by chromosome conformational capture(3C),the results were consistent with those of sequencing.The functional analysis of regulatory elements by formaldehyde-assisted separation regulatory elements and Epiregio online website showed that the screening sites AC105129.4,AL354707.17,AC078785.22 and AC021646.35 were all potential regulatory elements involved inβ-globin gene.Conclusion:The interaction between 4C screening site and anchor site showed the complex spatial organization ofβ-globin family loci in the nucleus.展开更多
Transposable elements(TEs)regularly capture fragments of genes.When the host silences these TEs,siRNAs homologous to the captured regions may also target the genes.This epigenetic crosstalk establishes an intragenomic...Transposable elements(TEs)regularly capture fragments of genes.When the host silences these TEs,siRNAs homologous to the captured regions may also target the genes.This epigenetic crosstalk establishes an intragenomic conflict:silencing the TEs has the cost of silencing the genes.If genes are important,however,natural selection may maintain function by moderating the silencing response,which may also advantage the TEs.In this study,we examined this model by focusing on Helitrons,Pack-MULEs,and Sirevirus LTR retrotransposons in the maize genome.We documented 1263 TEs containing exon fragments from 1629 donor genes.Consistent with epigenetic conflict,donor genes mapped more siRNAs and were more methylated than genes with no evidence of capture.However,these patterns differed between syntelog versus translocated donor genes.Syntelogs appeared to maintain function,as measured by gene expression,consistent with moderation of silencing for functionally important genes.Epigenetic marks did not spread beyond their captured regions and 24nt crosstalk siRNAs were linked with CHH methylation.Translocated genes,in contrast,bore the signature of silencing.They were highly methylated and less expressed,but also overrepresented among donor genes and located away from chromosomal arms,which suggests a link between capture and gene movement.Splitting genes into potential functional categories based on evolutionary constraint supported the synteny-based findings.TE families captured genes in different ways,but the evidence for their advantage was generally less obvious;nevertheless,TEs with captured fragments were older,mapped fewer siRNAs,and were slightly less methylated than TEs without captured fragments.Collectively,our results argue that TE capture triggers an intragenomic conflict that may not affect the function of important genes but may lead to the pseudogenization of less-constrained genes.展开更多
基金Fund Project:National Natural Science Foundation of China(No.31660318)High-level Talents Project of Hainan Natural Science Foundation(No.820RC638)Innovation Project for Graduate Students in Hainan Province(No.Hys2020-377)。
文摘Objective:Studies have shown thatβ-globin gene presents a selective expression transformation mechanism during development,and its upstream locus control region(LCR)regulates the expression pattern ofβ-globin gene family.To further explore the molecular network ofβ-globin gene expression regulation,other long-range regulatory elements that may be involved in the regulation ofβ-globin gene expression were screened and the dynamic regulation and transformation mechanism ofβ-globin gene was deeply studied.Methods:Promyelocytic cells were induced to differentiate by all-trans retinoic acid.β-globin gene promoter region and LCR were used as the target sites for circular chromosome conformational capture(4C)analysis.Through sequencing and regulatory element analysis,the sites interacting withβ-globin family loci were screened in the whole genome.Results:According to the results of 4C sequencing,the sites that interact with HBD promoter region and LCR were screened.Verified by chromosome conformational capture(3C),the results were consistent with those of sequencing.The functional analysis of regulatory elements by formaldehyde-assisted separation regulatory elements and Epiregio online website showed that the screening sites AC105129.4,AL354707.17,AC078785.22 and AC021646.35 were all potential regulatory elements involved inβ-globin gene.Conclusion:The interaction between 4C screening site and anchor site showed the complex spatial organization ofβ-globin family loci in the nucleus.
基金A.M.is supported by an EMBO Postdoctoral Fellowship ALTF 775-2017 and by HFSPO Fellowship LT000496/2018-LD.K.S.is supported by a Postdoctoral Fellowship from the National Science Foundation(NSF)Plant Genome Research Program(1609024)+1 种基金B.S.G.is supported by an NSF grant 1655808A.B.is supported by The Royal Society(award nos.UF160222 and RGF/R1/180006).
文摘Transposable elements(TEs)regularly capture fragments of genes.When the host silences these TEs,siRNAs homologous to the captured regions may also target the genes.This epigenetic crosstalk establishes an intragenomic conflict:silencing the TEs has the cost of silencing the genes.If genes are important,however,natural selection may maintain function by moderating the silencing response,which may also advantage the TEs.In this study,we examined this model by focusing on Helitrons,Pack-MULEs,and Sirevirus LTR retrotransposons in the maize genome.We documented 1263 TEs containing exon fragments from 1629 donor genes.Consistent with epigenetic conflict,donor genes mapped more siRNAs and were more methylated than genes with no evidence of capture.However,these patterns differed between syntelog versus translocated donor genes.Syntelogs appeared to maintain function,as measured by gene expression,consistent with moderation of silencing for functionally important genes.Epigenetic marks did not spread beyond their captured regions and 24nt crosstalk siRNAs were linked with CHH methylation.Translocated genes,in contrast,bore the signature of silencing.They were highly methylated and less expressed,but also overrepresented among donor genes and located away from chromosomal arms,which suggests a link between capture and gene movement.Splitting genes into potential functional categories based on evolutionary constraint supported the synteny-based findings.TE families captured genes in different ways,but the evidence for their advantage was generally less obvious;nevertheless,TEs with captured fragments were older,mapped fewer siRNAs,and were slightly less methylated than TEs without captured fragments.Collectively,our results argue that TE capture triggers an intragenomic conflict that may not affect the function of important genes but may lead to the pseudogenization of less-constrained genes.
