SOSHI-seq: a high-throughput screening assay to test the functionality of putative response elements for nuclear...

Area of Science:

• Molecular Biology
• Genomics
• Endocrinology

Background:

• Identifying functional hormone response elements is crucial for understanding gene regulation.
• Existing methods like ChIP-Seq identify occupied sites but not necessarily functional elements.
• Nuclear receptors play key roles in various physiological processes through hormone signaling.

Purpose of the Study:

• To present SOSHI-seq, a novel, cost-effective, and rapid assay for screening hormone-response elements.
• To demonstrate the utility of SOSHI-seq as a complement to ChIP-Seq for genome-wide identification of functional elements.
• To investigate thyroid hormone receptor binding sites using SOSHI-seq.

Main Methods:

• SOSHI-seq (Screening of Self-transcribed Hormone Inducible response elements coupled to sequencing) was developed as an adaptation of STARR-seq.
• The assay tests the capacity of thousands of synthetic DNA sequences to function as hormone-response elements.
• Thyroid hormone nuclear receptors were used as a model system to validate the assay.

Main Results:

• SOSHI-seq enables high-throughput screening of potential hormone-response elements.
• The assay successfully identified functional response elements for thyroid hormone receptors.
• SOSHI-seq data complements ChIP-Seq, providing functional validation of occupied genomic regions.

Conclusions:

• SOSHI-seq is a versatile and efficient tool for discovering functional hormone-response elements.
• The assay significantly enhances the ability to map nuclear receptor activity at a genome-wide scale.
• SOSHI-seq offers a valuable addition to the toolkit for studying hormone signaling and gene regulation.