相关实验视频

Updated: Sep 20, 2025

An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues

An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues

Published on: April 5, 2018

绘制黑色素相互作用在黑色素瘤易感部位的地图,揭示了遥远的cis调节基因点

Rohit Thakur¹, Mai Xu¹, Hayley Sowards¹

¹Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

American journal of human genetics

|May 23, 2025

概括

这项研究使用Capture-HiC将黑色素瘤风险变异与向基因联系起来,确定新的潜在因果基因和调节相互作用. 这些发现表明MDM4,CBL和SOX4与黑色素瘤的发展有关.

科学领域:

遗传学是一个遗传学.
基因组学就是基因组学.
癌症生物学癌症生物学

背景情况:

全基因组关联研究 (GWAS) 已经确定了与黑色素瘤风险相关的众多遗传位置.
大多数GWAS信号背后的特定功能变体和向基因在很大程度上是未知的.
了解这些遗传基础对于阐明黑色素瘤的发病过程至关重要.

研究的目的:

使用Capture-HiC.识别与黑色素瘤风险信号相关的功能变异和候选向基因.
整合多个功能性基因组数据集,以便对因果变异和基因进行强有力的优先排序.
在相关细胞模型中验证已识别的 cis 调节性相互作用.

主要方法:

在人类初级黑色素细胞中进行了捕获-HiC测定,重点关注黑色素瘤GWAS区域.
综合色素相互作用数据与表观基因组,基因表达 (eQTL/TWAS),DNA甲基化 (meQTL/MWAS) 和MPRA数据.
利用整合性评分系统和CRISPR抑制用于变异/基因优先级和相互作用验证.

主要成果:

染色体相互作用提名了68个黑色素瘤风险信号中的61个潜在的因果基因.
确定了140个优先级可信的因果变异,与42个风险信号的195个候选基因相关联.
验证了涉及已知癌症基因MDM4,CBL和SOX4.4的长距离cis调节相互作用.

结论:

捕获-HiC与多omics数据相结合,有效地将GWAS风险变异与候选黑色素瘤易感基因联系起来.
这种方法显著扩大了潜在的因果基因的范围,超出了之前的研究.
这些发现为MDM4,CBL和SOX4作为黑色素瘤风险基因提供了有力的证据,推动了我们对黑色素瘤遗传学的理解.

关键词:

这是CBL CBL.在GWAS中,GWAS就是GWAS.在MDM4DM4中使用.这就是SOX4的SOX4.捕获-HiC 的时间.黑色素瘤是一种黑色素瘤.

更多相关视频

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

Published on: March 8, 2022

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration

Published on: January 9, 2020

相关概念视频

Epigenetic Regulation

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...

Chromatin Position Affects Gene Expression

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...

Master Transcription Regulators

Master Transcription Regulators

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...