Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1.
Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1.
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DOI：
10.1038/ncomms7069
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发表时间：
2015-02-04
影响因子：
16.6
通讯作者：
Reddy TE
中科院分区：
文献类型：
--
作者：
Guo C;Ludvik AE;Arlotto ME;Hayes MG;Armstrong LL;Scholtens DM;Brown CD;Newgard CB;Becker TC;Layden BT;Lowe WL;Reddy TE
怀孕期间的母体葡萄糖水平影响发育中的胎儿，影响生命早期和后期的代谢健康。遗传和环境因素都会影响母体代谢，但对妊娠期间改变葡萄糖代谢的遗传机制知之甚少。在这里，我们报告说，单倍型以前与妊娠高血糖症在第三个三个月中断调节元件的活动，并减少附近的HKDC1基因的表达。我们进一步发现，实验减少或增加HKDC1的表达减少或增加己糖激酶的活性，分别在多种细胞模型中，纯化的HKDC1蛋白在体外具有己糖激酶活性。总之，这些结果表明了妊娠期葡萄糖调节的一种新机制，其中多个调节元件中的遗传变异的影响通过协调降低新型己糖激酶HKDC 1的表达来改变葡萄糖稳态。
Maternal glucose levels during pregnancy impact the developing fetus, affecting metabolic health early and later in life. Both genetic and environmental factors influence maternal metabolism, but little is known about the genetic mechanisms that alter glucose metabolism during pregnancy. Here we report that haplotypes previously associated with gestational hyperglycemia in the third trimester disrupt regulatory element activity and reduce expression of the nearby HKDC1 gene. We further find that experimentally reducing or increasing HKDC1 expression reduces or increases hexokinase activity, respectively, in multiple cellular models; and that purified HKDC1 protein has hexokinase activity in vitro. Together, these results suggest a novel mechanism of gestational glucose regulation in which the effects of genetic variants in multiple regulatory elements alter glucose homeostasis by coordinately reducing expression of the novel hexokinase HKDC1.
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影响因子：
64.8
作者：
通讯作者：
--
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Ng, PC;Henikoff, S
通讯作者：
Henikoff, S
影响因子：
3.5
作者：
Faletra, Flavio;Athanasakis, Emmanouil;Gasparini, Paolo
通讯作者：
Gasparini, Paolo
DOI：
10.1016/j.cbd.2007.11.002
发表时间：
2008-03-01
影响因子：
3
作者：
Irwin, David M.;Tan, Huanran
通讯作者：
Tan, Huanran