The Experts below are selected from a list of 60 Experts worldwide ranked by ideXlab platform
Véronique Lefebvre - One of the best experts on this subject based on the ideXlab platform.
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The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers
Nucleic acids research, 2015Co-Authors: Baojin Yao, Qiuqing Wang, Chia Feng Liu, Pallavi Bhattaram, Timothy J. Mead, James F. Crish, Véronique LefebvreAbstract:Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized Skeleton Malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. In contrast, the mechanisms whereby translocations in the –350/–50-kb region 5′ of SOX9 cause severe disease and whereby SOX9 expression is specified in chondrocytes remain scarcely known. We here screen this upstream region and uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9 expression domain. Three of them are primarily active in chondrocytes. E250 (located at –250 kb) confines its activity to condensed prechondrocytes, E195 mainly targets proliferating chondrocytes, and E84 is potent in all differentiated chondrocytes. E84 and E195 synergize with E70, previously shown to be active in most Sox9-expressing somatic tissues, including cartilage. While SOX9 protein powerfully activates E70, it does not control E250. It requires its SOX5/SOX6 chondrogenic partners to robustly activate E195 and additional factors to activate E84. Altogether, these results indicate that SOX9 expression in chondrocytes relies on widely spread transcriptional modules whose synergistic and overlapping activities are driven by SOX9, SOX5/SOX6 and other factors. They help elucidate mechanisms underlying campomelic dysplasia and will likely help uncover other disease mechanisms.
Baojin Yao - One of the best experts on this subject based on the ideXlab platform.
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The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers
Nucleic acids research, 2015Co-Authors: Baojin Yao, Qiuqing Wang, Chia Feng Liu, Pallavi Bhattaram, Timothy J. Mead, James F. Crish, Véronique LefebvreAbstract:Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized Skeleton Malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. In contrast, the mechanisms whereby translocations in the –350/–50-kb region 5′ of SOX9 cause severe disease and whereby SOX9 expression is specified in chondrocytes remain scarcely known. We here screen this upstream region and uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9 expression domain. Three of them are primarily active in chondrocytes. E250 (located at –250 kb) confines its activity to condensed prechondrocytes, E195 mainly targets proliferating chondrocytes, and E84 is potent in all differentiated chondrocytes. E84 and E195 synergize with E70, previously shown to be active in most Sox9-expressing somatic tissues, including cartilage. While SOX9 protein powerfully activates E70, it does not control E250. It requires its SOX5/SOX6 chondrogenic partners to robustly activate E195 and additional factors to activate E84. Altogether, these results indicate that SOX9 expression in chondrocytes relies on widely spread transcriptional modules whose synergistic and overlapping activities are driven by SOX9, SOX5/SOX6 and other factors. They help elucidate mechanisms underlying campomelic dysplasia and will likely help uncover other disease mechanisms.
Hui Zheng - One of the best experts on this subject based on the ideXlab platform.
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Mutant Human Presenilin 1 Protects presenilin 1 Null Mouse against Embryonic Lethality and Elevates Aβ1–42/43 Expression
Neuron, 1998Co-Authors: Su Qian, Ping Jiang, Xiao-ming Guan, Gurparkash Singh, Myrna E. Trumbauer, Howard Y. Chen, Lex H.t. Van Der Ploeg, Hui ZhengAbstract:Mutations in presenilin 1 (PS1) are linked to early onset of familial Alzheimer's disease (FAD) and are shown to foster production of Abeta1-42/43 in FAD patients and transgenic mice. PS1 null mice are embryonic lethal and exhibit axial Skeleton Malformation and CNS defects. We show that transgenic mouse lines expressing either the wild-type human PS1 protein or human PS1 with the A246E FAD mutation can rescue the PS1 knockout mouse from embryonic lethality to similar degrees, indicating that the mutation does not lead to loss of PS1 function during development. Furthermore, a 50% reduction of PS1 activity in PS1(+/-) mice does not lead to Abeta1-42/43 increase, whereas expression of human mutant PS1 on murine PS1 null background is sufficient to elevate Abeta1-42/43, supporting a gain-of-function activity as the result of the PS1 mutation.
Qiuqing Wang - One of the best experts on this subject based on the ideXlab platform.
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The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers
Nucleic acids research, 2015Co-Authors: Baojin Yao, Qiuqing Wang, Chia Feng Liu, Pallavi Bhattaram, Timothy J. Mead, James F. Crish, Véronique LefebvreAbstract:Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized Skeleton Malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. In contrast, the mechanisms whereby translocations in the –350/–50-kb region 5′ of SOX9 cause severe disease and whereby SOX9 expression is specified in chondrocytes remain scarcely known. We here screen this upstream region and uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9 expression domain. Three of them are primarily active in chondrocytes. E250 (located at –250 kb) confines its activity to condensed prechondrocytes, E195 mainly targets proliferating chondrocytes, and E84 is potent in all differentiated chondrocytes. E84 and E195 synergize with E70, previously shown to be active in most Sox9-expressing somatic tissues, including cartilage. While SOX9 protein powerfully activates E70, it does not control E250. It requires its SOX5/SOX6 chondrogenic partners to robustly activate E195 and additional factors to activate E84. Altogether, these results indicate that SOX9 expression in chondrocytes relies on widely spread transcriptional modules whose synergistic and overlapping activities are driven by SOX9, SOX5/SOX6 and other factors. They help elucidate mechanisms underlying campomelic dysplasia and will likely help uncover other disease mechanisms.
James F. Crish - One of the best experts on this subject based on the ideXlab platform.
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The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers
Nucleic acids research, 2015Co-Authors: Baojin Yao, Qiuqing Wang, Chia Feng Liu, Pallavi Bhattaram, Timothy J. Mead, James F. Crish, Véronique LefebvreAbstract:Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized Skeleton Malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. In contrast, the mechanisms whereby translocations in the –350/–50-kb region 5′ of SOX9 cause severe disease and whereby SOX9 expression is specified in chondrocytes remain scarcely known. We here screen this upstream region and uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9 expression domain. Three of them are primarily active in chondrocytes. E250 (located at –250 kb) confines its activity to condensed prechondrocytes, E195 mainly targets proliferating chondrocytes, and E84 is potent in all differentiated chondrocytes. E84 and E195 synergize with E70, previously shown to be active in most Sox9-expressing somatic tissues, including cartilage. While SOX9 protein powerfully activates E70, it does not control E250. It requires its SOX5/SOX6 chondrogenic partners to robustly activate E195 and additional factors to activate E84. Altogether, these results indicate that SOX9 expression in chondrocytes relies on widely spread transcriptional modules whose synergistic and overlapping activities are driven by SOX9, SOX5/SOX6 and other factors. They help elucidate mechanisms underlying campomelic dysplasia and will likely help uncover other disease mechanisms.