cis-监管要素对人类细分重复的表达差异的影响
Colin J Shew1,2, Gulhan Kaya1, Sean P McGinty1
1Genome Center, University of California, Davis, CA, USA.
bioRxiv : the preprint server for biology
|November 26, 2025
概括
人类特异性细分重复 (HSD) 显示了监管分歧,重复的元素表现出改变的活动. 这些变化,特别是在 cis 调节元件 (CREs) 中,有助于人类特异性特征和基因表达模式.
科学领域:
- 基因组学就是基因组学.
- 进化生物学 进化生物学
- 调控生物学 调控生物学
背景情况:
- 人类特异性细分重复 (HSD) 代表了独特的基因组区域,其中的基因对神经发育至关重要.
- 尽管它们最近的进化起源 (<600万年),但HSD基因表现出显著的调节分歧和对应物特异性表达.
研究的目的:
- 在HSD中系统地表征cis-regulatory元素 (CREs).
- 了解最近进化的基因家族中的调控变化及其对人类特异性特征的贡献.
主要方法:
- 在7160个人类重复和黑猩猩正统序列上进行了大规模的并行记者分析.
- 使用的淋巴状细胞 (GM12878) 和神经母细胞瘤 (SH-SY5Y) 细胞系用于记者测定.
- 综合长读表达和表观基因组数据.
主要成果:
- 14-24%的序列显示了人类和黑猩猩 ортолог之间或人类对应物之间的差异性活性.
- 预测的 cis调节性活性差异与SH-SY5Y细胞中的mRNA水平相关.
- 在CHRFAM7A,HYDIN2和SRGAP2C等基因中验证了差异活性CREs.
结论:
- 重复的CREs的功能分歧对HSD基因的调节分歧有适度的贡献.
- 改变基因组的位置效应可能在监管分歧中发挥重要作用.
- 确定增强剂作为人类特异性监管模式的潜在驱动因素.
更多相关视频
11:36Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
Published on: April 21, 2023
2.9K
08:19Quantitative Comparison of cis-Regulatory Element CRE Activities in Transgenic Drosophila melanogaster
Published on: December 19, 2011
12.2K
相关概念视频
Cis-regulatory Sequences
11.5K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.5K
Cis-regulatory Sequences
4.0K
4.0K
Gene Duplication and Divergence
7.8K
The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
7.8K
Cooperative Binding of Transcription Regulators
7.1K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.1K
Regulation of Expression at Multiple Steps
1.3K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.3K
Multi-species Conserved Sequences
4.6K
Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
4.6K
