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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Genome-wide analysis of SREBP-1 binding in mouse liver chromatin reveals a preference for promoter proximal binding to a new motif
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Genome-wide analysis of SREBP-1 binding in mouse liver chromatin reveals a preference for promoter proximal binding to a new motif

机译:小鼠肝染色质中SREBP-1结合的全基因组分析揭示了对启动子近端结合新基序的偏好

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摘要

Lipid homeostasis in vertebrates is regulated by 3 sterol regulatory element binding protein (SREBP) isoforms. Here, we identify targets of SREBP-1 in mammalian liver using chromatin immunopre-cipitation-high-throughput DNA sequencing. Antisera to SREBP-1 were used with liver chromatin from mice fed a high-carbohydrate diet after a fast, which leads to superinduction of hepatic SREBP-1c expression. SREBP-1-DNA complexes were subjected to massive parallel DNA sequencing using the Illumina Genome Analyzer II, resulting in 5.7 million sequence reads. Mapping these reads to the mouse reference genome identified 426 peaks of SREBP-1 binding vs. a control antibody. These binding peaks show a striking enrichment in proximal promoter regions, with 52% located within 1 kb upstream of a transcription start site. A previously unde-scribed sequence motif (5'-ACTACANNTCCC-3') was present in 76% of the total peaks, and we show that it is a functional SREBP-1 response element. Our analysis also reveals that an Sp1 consensus site is present as a "coregulatory" motif in 50% of the SREBP-1 binding peaks, consistent with previous functional studies. SREBP-1 bound not only to many well-characterized SREBP-1 target genes but to several other previously unknown targets in lipid and carbohydrate metabolism as well as many putative target genes in other diverse biological pathways.
机译:脊椎动物的脂质稳态由3种固醇调节元件结合蛋白(SREBP)同工型调节。在这里,我们使用染色质免疫沉淀-高通量DNA测序鉴定哺乳动物肝脏中SREBP-1的靶标。对SREBP-1的抗血清与禁食后喂食高碳水化合物饮食的小鼠的肝脏染色质一起使用,这会导致肝SREBP-1c表达的超诱导。使用Illumina Genome Analyzer II对SREBP-1-DNA复合物进行大规模并行DNA测序,获得570万个序列读数。将这些读数映射到小鼠参考基因组可确定与对照抗体相比,SREBP-1结合的426个峰。这些结合峰在近端启动子区域显示出惊人的富集,其中52%位于转录起始位点上游1 kb以内。之前未描述的序列基序(5'-ACTACANNTCCC-3')存在于总峰的76%中,我们证明它是功能性SREBP-1响应元件。我们的分析还揭示了Sp1共有位点在50%的SREBP-1结合峰中以“可调节”基序形式存在,与以前的功能研究一致。 SREBP-1不仅与许多特征明确的SREBP-1靶基因结合,而且还与脂质和碳水化合物代谢中的其他几个先前未知的靶标以及其他多种生物学途径中的许多推定的靶基因结合。

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  • 作者单位

    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697;

    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 Institute for Genomics and Bioinformatics, University of California, Irvine, CA 92697;

    Institute for Genomics and Bioinformatics, University of California, Irvine, CA 92697 Department of Computer Science, University of California, Irvine, CA 92697;

    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697;

    Institute for Genomics and Bioinformatics, University of California, Irvine, CA 92697 Department of Computer Science, University of California, Irvine, CA 92697;

    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    ChlP-seq; fasting/refeeding; Sp1; kolmogorov-smirnov test;

    机译:ChlP-seq;禁食/喂食;Sp1;科尔莫哥罗夫-斯米尔诺夫检验;

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