综合生物信息学分析揭示了内皮细胞中的转录因子EB驱动的微RNA调控网络
Teresa Gravina1,2, Francesco Favero1,2, Stefania Rosano3,4
1Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.
International journal of molecular sciences
|July 13, 2024
概括
转录因子EB (TFEB) 调节内皮细胞功能和血管健康. 这项研究揭示了TFEB直接控制microRNAs,扩大其在血管生物学和疾病治疗中的调节作用.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 血管生物学 血管生物学
背景情况:
- 转录因子,如转录因子EB (TFEB),是细胞过程的关键调节者,与人类疾病相关的不平衡.
- TFEB在内皮细胞 (ECs) 中起着至关重要的作用,维护血管完整性和功能.
- 整个由TFEB管理的监管网络,特别是在EC中,尚未完全理解.
研究的目的:
- 阐明TFEB在人类静脉内皮细胞 (HUVECs) 中协调的综合性调节网络.
- 揭示新的机制性见解,了解TFEB如何影响ECs内的转录格局.
- 通过TFEB识别微RNA (miRNA) 介导的基因调节.
主要方法:
- 综合生物信息学分析,结合高通量实验数据.
- 在异位表达TFEB的HUVEC中进行染色体免疫沉降测序 (ChIP-seq).
- 在TFEB沉默型HUVEC中测序多基化mRNA和小RNA.
- 开发一个生物信息学管道,绘制TFEB驱动的基因调节相互作用.
主要成果:
- TFEB直接调节多个微RNAs (miRNAs) 的表达.
- 这些TFEB调节的miRNAs在转录后调节一个广泛的目标基因网络.
- 这揭示了TFEB影响的基因程序的扩展范围,超出了直接的转录标.
结论:
- TFEB通过直接调节miRNA来对内皮细胞功能进行调控控制.
- 这些发现大大拓宽了我们对TFEB在血管生物学中的作用的理解.
- 这项工作为开发针对血管疾病的新疗法提供了基础,通过调节TFEB-miRNA轴来调节血管疾病.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
01:22MicroRNAs
21.3K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
21.3K
02:23Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K