Prediction of mammalian tissue-specific CLOCK-BMAL1 binding to E-box DNA motifs.
Prediction of mammalian tissue-specific CLOCK-BMAL1 binding to E-box DNA motifs.
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DOI：
10.1038/s41598-023-34115-w
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发表时间：
2023-05-12
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
大脑和肌肉类似ARNTL的1蛋白（BMAL1）形成昼夜节律运动循环（时钟）或神经元PAS蛋白2（NPAS2）的异二聚体，以充当哺乳动物昼夜节律的主调节器与DNA上的E-Box基因调节元件结合，激活了时钟基因的下游转录。鉴于Clock – BMAL1或NPAS2 – BMAL1与DNA上的几个不同类型的机器学习模型在DNA上结合了几个不同的结合基序（CANNTG），BMAL1与DNA结合是一个挑战问题。 DNA序列，（2）DNA序列加上DNA形状，（3）DNA序列和形状以及组蛋白修饰，我们开发了全基因组的可解释预测模型BMAL1与E-Box基序结合并解剖BMAL1-DNA的基础机制，表明我们的结果表明组蛋白的修饰，DNA的局部形状和E-box基序的侧翼序列是BMAL1-DNA结合的充分预测性我们的模型还提供了BMAL1的DNA结合的组织特异性的机械见解。
The Brain and Muscle ARNTL-Like 1 protein (BMAL1) forms a heterodimer with either Circadian Locomotor Output Cycles Kaput (CLOCK) or Neuronal PAS domain protein 2 (NPAS2) to act as a master regulator of the mammalian circadian clock gene network. The dimer binds to E-box gene regulatory elements on DNA, activating downstream transcription of clock genes. Identification of transcription factor binding sites and genomic features that correlate to DNA binding by BMAL1 is a challenging problem, given that CLOCK–BMAL1 or NPAS2–BMAL1 bind to several distinct binding motifs (CANNTG) on DNA. Using three different types of tissue-specific machine learning models with features based on (1) DNA sequence, (2) DNA sequence plus DNA shape, and (3) DNA sequence and shape plus histone modifications, we developed an interpretable predictive model of genome-wide BMAL1 binding to E-box motifs and dissected the mechanisms underlying BMAL1–DNA binding. Our results indicated that histone modifications, the local shape of the DNA, and the flanking sequence of the E-box motif are sufficient predictive features for BMAL1–DNA binding. Our models also provide mechanistic insights into tissue specificity of DNA binding by BMAL1.
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影响因子：
10.5
作者：
Menet JS;Pescatore S;Rosbash M
通讯作者：
Rosbash M
影响因子：
14.9
作者：
Li J;Sagendorf JM;Chiu TP;Pasi M;Perez A;Rohs R
通讯作者：
Rohs R
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
7
作者：
Dror I;Golan T;Levy C;Rohs R;Mandel-Gutfreund Y
通讯作者：
Mandel-Gutfreund Y
DOI：
10.1093/bioinformatics/btv735
发表时间：
2016-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Chiu TP;Comoglio F;Zhou T;Yang L;Paro R;Rohs R
通讯作者：
Rohs R