The adrenergic receptor kinase 1 (ADRBK1), thromboxane A2 receptor (TBXA2R) and vascular endothelial growth factor (VEGFA) regulatory (r) single nucleotide polymorphisms (SNPs) found in the potential stimulating prote...The adrenergic receptor kinase 1 (ADRBK1), thromboxane A2 receptor (TBXA2R) and vascular endothelial growth factor (VEGFA) regulatory (r) single nucleotide polymorphisms (SNPs) found in the potential stimulating protein-1 (SP1) and Kruppel-like factor-4 (KLF4) transcriptional factor binding sites (TFBS) within these genes are in linkage disequilibrium (LD). The LD may result from rSNP alleles that create TFBS for the KLF4 and SP1 transcriptional factors (TF) since the alternate rSNP alleles do not create these TFBS. Consequently, haplotypes carrying the rSNP alleles that create KLF4 and SP1 TFBS are essential for ADRBK1, TBXA2R and VEGFA gene regulation by these TFs.展开更多
The rSNPs for the genes AKT3 (rs4590656), EGLN1 (rs480902), eNOS3 (rs1007311), and VEGFA (rs699947, rs13207311, rs1570360, rs2010963) have been significantly associated with the physiological parameters in high altitu...The rSNPs for the genes AKT3 (rs4590656), EGLN1 (rs480902), eNOS3 (rs1007311), and VEGFA (rs699947, rs13207311, rs1570360, rs2010963) have been significantly associated with the physiological parameters in high altitude sickness Han or Tibetan Chinese patients at the Qinghai-Tibetan plateau. The alleles of each rSNP have been found to create unique transcriptional factor binding sites for transcription factors that affect the process of hypoxia gene expression in this high altitude hypoxia environment.展开更多
Three rSNPs (rs3125289, rs1877474 and rs11119982) in one intron of the activating transcription factor 3 (ATF3) gene have been significantly associated with the human etiology of hypospadias and may be associated with...Three rSNPs (rs3125289, rs1877474 and rs11119982) in one intron of the activating transcription factor 3 (ATF3) gene have been significantly associated with the human etiology of hypospadias and may be associated with human disease. These rSNP alleles alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in transcriptional factor binding sites (TFBS). These TFBS changes are examined with respect to the human etiology of hypospadias which has been found to be significantly associated with the rSNPs.展开更多
Four regulatory single nucleotide polymorphisms (rSNPs) (rs2238631, rs2238632, rs2238633 and rs2238634) in intron one, two rSNPs (rs1131882 and rs4523) in exon 3 and one rSNP (rs5756) in the 3’UTR of the thromboxane ...Four regulatory single nucleotide polymorphisms (rSNPs) (rs2238631, rs2238632, rs2238633 and rs2238634) in intron one, two rSNPs (rs1131882 and rs4523) in exon 3 and one rSNP (rs5756) in the 3’UTR of the thromboxane A2 receptor (TBXA2R) gene have been associated with childhood-onset asthma in Asians. These rSNP alleles alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in transcriptional factor binding sites (TFBS). These TFBS changes are examined with respect to asthma which has been found to be significantly associated with the rSNPs.展开更多
Seven rSNPs (rs10157763, rs10927067, rs12031994, rs2125230, rs2345994, rs4132509 and rs4590646) in intron one of thev-akt murine thymoma viral oncogene homolog 3 (AKT3) gene have been significantly associated with eit...Seven rSNPs (rs10157763, rs10927067, rs12031994, rs2125230, rs2345994, rs4132509 and rs4590646) in intron one of thev-akt murine thymoma viral oncogene homolog 3 (AKT3) gene have been significantly associated with either Chronic Mountain Sickness, Renal Cell Carcinoma risk or Aggressive Prostate Cancer. These rSNP alleles alter the DNA landscape for potential transcriptional factors (TFs)?to attach, resulting in changes in transcriptional factor binding sites (TFBS). The alleles of each rSNP were found to produce unique TFBS resulting in potential changes in TF AKT3 regulation. These regulatory changes are discussed with respect to the three diseases.展开更多
Single nucleotide polymorphisms (SNPs) located in the PPARα/δ/γ genes that have been previously found to be significantly associated with human disease or a condition were also found to alter the genes punitive tra...Single nucleotide polymorphisms (SNPs) located in the PPARα/δ/γ genes that have been previously found to be significantly associated with human disease or a condition were also found to alter the genes punitive transcriptional factor binding sites (TFBS). Two alleles (C/G) of the PPARα SNP (rs1800206) were found to generate 7 common and 8 unique punitive TFBS. One of the unique TFBS created by the minor G (0.02) allele is for the T-Box 4 (TBX4) transcription factor which is associated with heritable pulmonary arterial hypertension. Two alleles (A/G) of the PPARδ SNP (rs2016520) were found to generate 20 unique punitive TFBS while the two alleles (C/G) of the PPARδ SNP (rs9794) were found to generate 11 common and 11unique punitive TFBS. The alleles of the PPARγ SNPs (rs10865710, rs12629751, rs709158, rs1805192 and rs3856806) were found to generate 15, 12, 16, 2 and 21 common and 9, 4, 12, 4 and 7 unique punitive TFBS, respectively. These changes in TFBS are discussed with relation to alterations in gene expression that may result in disease or change in human condition.展开更多
Xanthomonas bacteria secrete transcription activator-like effector(TALE)proteins into host cells to activate plant disease susceptibility genes to cause disease,and the process is dependent on interaction between bact...Xanthomonas bacteria secrete transcription activator-like effector(TALE)proteins into host cells to activate plant disease susceptibility genes to cause disease,and the process is dependent on interaction between bacteria TFB domain of TALEs and host plant basal transcription factor IIA gamma subunit(TFIIAγ).The key domain or residues of plant TFIIAγand core residues of bacteria TFB domain that are indispensable for TFIIAγ-TALEs interaction in the process of TALE-carrying Xanthomonas invasion plants are unknown.Here,we showed that the thirdα-helix domain of OsTFIIAγ5/Xa5,especially the 38th,39th,40th and 42th residues were key sites for capturing by TALEs of Xanthomonas oryzae pv.oryzae(Xoo),the causal agent of rice bacterial blight disease.The latter segment of Xoo TFB domain harboring seventy-two amino acid residues was vital for TALE specific binding with host plant OsTFIIAγ5/Xa5.Substitution of some residues in this core region of TFB domain completely compromised capacity of TALEs capturing rice OsTFIIAγ5/Xa5.The rich and conserved arginine residues in this core region of TFB domain were responsible for TALE-dependent plant susceptibility gene activation and virulence of Xoo.These results provide a potential strategy for improving resistance to TALE-carrying pathogens in plants by site-specific modification of key residues of host plant TFIIAγ.展开更多
文摘The adrenergic receptor kinase 1 (ADRBK1), thromboxane A2 receptor (TBXA2R) and vascular endothelial growth factor (VEGFA) regulatory (r) single nucleotide polymorphisms (SNPs) found in the potential stimulating protein-1 (SP1) and Kruppel-like factor-4 (KLF4) transcriptional factor binding sites (TFBS) within these genes are in linkage disequilibrium (LD). The LD may result from rSNP alleles that create TFBS for the KLF4 and SP1 transcriptional factors (TF) since the alternate rSNP alleles do not create these TFBS. Consequently, haplotypes carrying the rSNP alleles that create KLF4 and SP1 TFBS are essential for ADRBK1, TBXA2R and VEGFA gene regulation by these TFs.
文摘The rSNPs for the genes AKT3 (rs4590656), EGLN1 (rs480902), eNOS3 (rs1007311), and VEGFA (rs699947, rs13207311, rs1570360, rs2010963) have been significantly associated with the physiological parameters in high altitude sickness Han or Tibetan Chinese patients at the Qinghai-Tibetan plateau. The alleles of each rSNP have been found to create unique transcriptional factor binding sites for transcription factors that affect the process of hypoxia gene expression in this high altitude hypoxia environment.
文摘Three rSNPs (rs3125289, rs1877474 and rs11119982) in one intron of the activating transcription factor 3 (ATF3) gene have been significantly associated with the human etiology of hypospadias and may be associated with human disease. These rSNP alleles alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in transcriptional factor binding sites (TFBS). These TFBS changes are examined with respect to the human etiology of hypospadias which has been found to be significantly associated with the rSNPs.
文摘Four regulatory single nucleotide polymorphisms (rSNPs) (rs2238631, rs2238632, rs2238633 and rs2238634) in intron one, two rSNPs (rs1131882 and rs4523) in exon 3 and one rSNP (rs5756) in the 3’UTR of the thromboxane A2 receptor (TBXA2R) gene have been associated with childhood-onset asthma in Asians. These rSNP alleles alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in transcriptional factor binding sites (TFBS). These TFBS changes are examined with respect to asthma which has been found to be significantly associated with the rSNPs.
文摘Seven rSNPs (rs10157763, rs10927067, rs12031994, rs2125230, rs2345994, rs4132509 and rs4590646) in intron one of thev-akt murine thymoma viral oncogene homolog 3 (AKT3) gene have been significantly associated with either Chronic Mountain Sickness, Renal Cell Carcinoma risk or Aggressive Prostate Cancer. These rSNP alleles alter the DNA landscape for potential transcriptional factors (TFs)?to attach, resulting in changes in transcriptional factor binding sites (TFBS). The alleles of each rSNP were found to produce unique TFBS resulting in potential changes in TF AKT3 regulation. These regulatory changes are discussed with respect to the three diseases.
文摘Single nucleotide polymorphisms (SNPs) located in the PPARα/δ/γ genes that have been previously found to be significantly associated with human disease or a condition were also found to alter the genes punitive transcriptional factor binding sites (TFBS). Two alleles (C/G) of the PPARα SNP (rs1800206) were found to generate 7 common and 8 unique punitive TFBS. One of the unique TFBS created by the minor G (0.02) allele is for the T-Box 4 (TBX4) transcription factor which is associated with heritable pulmonary arterial hypertension. Two alleles (A/G) of the PPARδ SNP (rs2016520) were found to generate 20 unique punitive TFBS while the two alleles (C/G) of the PPARδ SNP (rs9794) were found to generate 11 common and 11unique punitive TFBS. The alleles of the PPARγ SNPs (rs10865710, rs12629751, rs709158, rs1805192 and rs3856806) were found to generate 15, 12, 16, 2 and 21 common and 9, 4, 12, 4 and 7 unique punitive TFBS, respectively. These changes in TFBS are discussed with relation to alterations in gene expression that may result in disease or change in human condition.
基金supported by the grants from the National Natural Science Foundation of China (31822042 and 31871946)the Fundamental Research Funds for the Central Universities, China (2662016PY020 and 2662017PY014)
文摘Xanthomonas bacteria secrete transcription activator-like effector(TALE)proteins into host cells to activate plant disease susceptibility genes to cause disease,and the process is dependent on interaction between bacteria TFB domain of TALEs and host plant basal transcription factor IIA gamma subunit(TFIIAγ).The key domain or residues of plant TFIIAγand core residues of bacteria TFB domain that are indispensable for TFIIAγ-TALEs interaction in the process of TALE-carrying Xanthomonas invasion plants are unknown.Here,we showed that the thirdα-helix domain of OsTFIIAγ5/Xa5,especially the 38th,39th,40th and 42th residues were key sites for capturing by TALEs of Xanthomonas oryzae pv.oryzae(Xoo),the causal agent of rice bacterial blight disease.The latter segment of Xoo TFB domain harboring seventy-two amino acid residues was vital for TALE specific binding with host plant OsTFIIAγ5/Xa5.Substitution of some residues in this core region of TFB domain completely compromised capacity of TALEs capturing rice OsTFIIAγ5/Xa5.The rich and conserved arginine residues in this core region of TFB domain were responsible for TALE-dependent plant susceptibility gene activation and virulence of Xoo.These results provide a potential strategy for improving resistance to TALE-carrying pathogens in plants by site-specific modification of key residues of host plant TFIIAγ.