The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.
The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.
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21三体对DNA甲基化的全基因组影响及其对造血的意义
DOI：
10.1038/s41467-021-21064-z
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发表时间：
2021-02-05
影响因子：
16.6
通讯作者：
de Smith AJ
中科院分区：
文献类型：
--
作者：
Muskens IS;Li S;Jackson T;Elliot N;Hansen HM;Myint SS;Pandey P;Schraw JM;Roy R;Anguiano J;Goudevenou K;Siegmund KD;Lupo PJ;de Bruijn MFTR;Walsh KM;Vyas P;Ma X;Roy A;Roberts I;Wiemels JL;de Smith AJ
唐氏综合征与全基因组范围的基因表达紊乱有关，这可能是由表观遗传学变化所介导的。我们对196名患有唐氏综合症的新生儿和439名非唐氏综合症的新生儿进行了表观基因组范围的关联研究，调整了细胞类型的异质性，确定了652个表观基因组显著的CPG(P <； 7.67 × 10−8)和1,052个差异甲基化区域。唐氏综合征与非唐氏综合征胎肝造血干/祖细胞在启动子/增强子区域的差异甲基化与基因表达变化相关(P <； 0.0001)。最上面的两个差异甲基化区域重叠在RUNX1和FLI1上，这两个区域都是巨核生成和造血发育的重要调节因子，这两个基因的启动子区域存在显著的高甲基化。排除具有白血病前GATA1突变的唐氏综合征新生儿(N = 30)，通过靶向测序确定，对表观基因组范围的关联研究结果影响最小。唐氏综合征对早期造血细胞的DNA甲基化有深远的全基因组影响，这可能是唐氏综合征儿童血液系统问题(包括白血病)高发的原因之一。唐氏综合征与免疫和造血系统疾病并存，发病率较高。在这里，作者在患有和不患有唐氏综合症的新生儿中进行了一项表观基因组范围的关联研究，以发现整个基因组中的差异甲基化，包括在造血调控因子RUNX1和FLI1中。
Down syndrome is associated with genome-wide perturbation of gene expression, which may be mediated by epigenetic changes. We perform an epigenome-wide association study on neonatal bloodspots comparing 196 newborns with Down syndrome and 439 newborns without Down syndrome, adjusting for cell-type heterogeneity, which identifies 652 epigenome-wide significant CpGs (P < 7.67 × 10−8) and 1,052 differentially methylated regions. Differential methylation at promoter/enhancer regions correlates with gene expression changes in Down syndrome versus non-Down syndrome fetal liver hematopoietic stem/progenitor cells (P < 0.0001). The top two differentially methylated regions overlap RUNX1 and FLI1, both important regulators of megakaryopoiesis and hematopoietic development, with significant hypermethylation at promoter regions of these two genes. Excluding Down syndrome newborns harboring preleukemic GATA1 mutations (N = 30), identified by targeted sequencing, has minimal impact on the epigenome-wide association study results. Down syndrome has profound, genome-wide effects on DNA methylation in hematopoietic cells in early life, which may contribute to the high frequency of hematological problems, including leukemia, in children with Down syndrome. Down syndrome has a high co-morbidity with immune and hematopoietic disorders. Here, the authors perform an epigenome-wide association study in newborns with and without Down syndrome to find differential methylation across the genome, including in hematopoietic regulators RUNX1 and FLI1.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
SENP1通过GATA1和MONGE病的受试者通过GATA1和BCL-XL诱导低氧诱导的多性性疾病。
DOI：
10.1084/jem.20151920
发表时间：
2016-11-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Azad P;Zhao HW;Cabrales PJ;Ronen R;Zhou D;Poulsen O;Appenzeller O;Hsiao YH;Bafna V;Haddad GG
通讯作者：
Haddad GG
影响因子：
7.7
作者：
Bergiers I;Andrews T;Vargel Bölükbaşı Ö;Buness A;Janosz E;Lopez-Anguita N;Ganter K;Kosim K;Celen C;Itır Perçin G;Collier P;Baying B;Benes V;Hemberg M;Lancrin C
通讯作者：
Lancrin C
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA