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MAE-seq refines regulatory elements across the genome

ABSTRACT: Proper cell fate determination relies on precise spatial and temporal genome-wide cooperativities among regulatory elements (REs) and their targeted genes. However, the lengths of REs defined by different methods are varied, which indicates sequence redundancy contained and the context of the genome will be unintelligible. To figure this out, we developed a method termed as MAE-seq (Massive Active Enhancers by Sequencing) to experimentally identify functional REs at a 25-bp scale. In this study, more than 626,879 active enhancers are identified in mouse embryonic stem cells. Comparative analysis indicates most of histone modification datasets could be annotated by MAE-Seq loci. Additionally, 35.03% (219,623) are identified as de novo ones without any epigenetic modification. Validation results show that these 25-bp sequences could act as a functional unit, which shows identical or similar expression patterns as the previously defined larger elements. Additionally, we examined the functions of some novel elements that can up-regulate gene activities. By integrating with Hi-C data, over 55.64% novel elements may have distal association with different targeted genes. As an example, we find Cdh1 gene is interacting with one novel and two known REs in mESCs. And their biological effects are investigated via CRISPR-Cas9. It indicates these distal associations can coordinate Cdh1 gene expression and mESCs proliferation. Therefore, our study provides an experimental approach to refine the REs at 25-bp resolution and it will be a great improvement to unscramble the underlying genome context.

ORGANISM(S): blank sample Mus musculus Homo sapiens

PROVIDER: GSE193494 | GEO | 2023/01/06

REPOSITORIES: GEO

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Refine regulatory elements across the genome

Project description:We develop an experimental method termed as MAE-seq, to identify active enhancer across the genome. Enhancer loci are mapped precisely to 25 bp in different types of cells. In mouse embryonic stem cells, 19,514 active enhancers are identified including 49.25% known and 50.75% de novo ones. In human HEK293T cell , 3,0359 active enhancers are identified.

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Project description:MAE-seq refines regulatory elements across the genome

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