The common oncogenomic program of NOTCH1 and NOTCH3 signaling in T-cell acute lymphoblastic leukemia.
The common oncogenomic program of NOTCH1 and NOTCH3 signaling in T-cell acute lymphoblastic leukemia.
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DOI：
10.1371/journal.pone.0185762
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Blacklow SC
中科院分区：
文献类型：
--
作者：
Choi SH;Severson E;Pear WS;Liu XS;Aster JC;Blacklow SC
Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL), in part because it binds to an enhancer that increases expression of MYC. Here, we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite substantial divergence in their intracellular regions, as a means to elucidate a broad, common Notch-dependent oncogenomic program through systematic comparison of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and NOTCH3-dependent T-ALL cells. ChIP-seq studies show a high concordance of functional NOTCH1 and NOTCH3 genomic binding sites that are enriched in binding motifs for RBPJ, the transcription factor that recruits activated Notch to DNA. The interchangeability of NOTCH1 and NOTCH3 was confirmed by rescue of NOTCH1-dependent T-ALL cells with activated NOTCH3 and vice versa. Despite remarkable overall similarity, there are nuanced differences in chromatin landscapes near critical common Notch target genes, most notably at a Notch-dependent enhancer that regulates MYC, which correlates with responsiveness to Notch pathway inhibitors. Overall, a common oncogenomic program driven by binding of either Notch is sufficient to maintain T-ALL cell growth, whereas cell-context specific differences appear to influence the response of T-ALL cells to Notch inhibition.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1073/pnas.0606108103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Palomero, Teresa;Lim, Wei Keat;Ferrando, Adolfo A.
通讯作者：
Ferrando, Adolfo A.
影响因子：
20.3
作者：
Nakagawa, Masahiro;Ichikawa, Motoshi;Chiba, Shigeru
通讯作者：
Chiba, Shigeru
影响因子：
50.3
作者：
Roti G;Carlton A;Ross KN;Markstein M;Pajcini K;Su AH;Perrimon N;Pear WS;Kung AL;Blacklow SC;Aster JC;Stegmaier K
通讯作者：
Stegmaier K