糖尿病相关最新一篇文章

大猪小猪落玉盘

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Intrauterine growth retardation (IUGR) has been linked to the onset of diseases in adulthood, including type" D9 v6 L) ^& C/ X& ?. K4 t6 a
2 diabetes, and has been proposed to result from altered gene regulation patterns due to epigenetic modifications6 S; `+ D( M; q  \
of developmental genes. To determine whether epigenetic modifications may play a role in the development, ]- ?0 h% g# x, m; j" N( M9 a. [
of adult diabetes following IUGR, we used a rodent model of IUGR that expresses lower levels of Pdx1, a- D# l2 ~. l7 L  r5 J, P/ @
pancreatic and duodenal homeobox 1 transcription factor critical for β cell function and development, which- x$ x- h' g( ~  {% M
develops diabetes in adulthood. We found that expression of Pdx1 was permanently reduced in IUGR β cells
- c$ @$ j7 l% iand underwent epigenetic modifications throughout development. The fetal IUGR state was characterized by2 S) f) D& l, i* T8 H, W! S
loss of USF-1 binding at the proximal promoter of Pdx1, recruitment of the histone deacetylase 1 (HDAC1) and' u7 I: p  C9 D" ^8 l. N
the corepressor Sin3A, and deacetylation of histones H3 and H4. Following birth, histone 3 lysine 4 (H3K4)2 |2 D* p& L& f
was demethylated and histone 3 lysine 9 (H3K9) was methylated. During the neonatal period, these epigenetic
( Z  l1 P' ~7 }1 hchanges and the reduction in Pdx1 expression could be reversed by HDAC inhibition. After the onset of diabetes
% {! Z& ^1 ~, y4 a3 qin adulthood, the CpG island in the proximal promoter was methylated, resulting in permanent silencing) u% E, B& d) C) }# w
of the Pdx1 locus. These results provide insight into the development of type 2 diabetes following IUGR and we8 v/ m$ i/ e- ~8 r' q
believe they are the first to describe the ontogeny of chromatin remodeling in vivo from the fetus to the onset
) M+ w( T8 c$ H8 Eof disease in adulthood.
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cdcliwei

Well done!

xiaomao_zhoubo

支持

jimzhua

谢谢

missyoudad

谢谢分享

w1986725

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荷荷

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