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Updated: Jul 23, 2025

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC Crosslinking of Small Molecules to Isolate Chromatin
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人类核受体对DNA结合的隐藏模式

Devesh Bhimsaria1, José A Rodríguez-Martínez2, Jacqui L Mendez-Johnson3

  • 1Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, 247667, India. devesh.bhimsaria@bt.iitr.ac.in.

Nature communications
|July 13, 2023
PubMed
概括

人类核受体 (NRs) 控制细胞功能和疾病. 这项研究使用SELEX和新算法绘制NR DNA结合部位的地图,揭示了与疾病相关的部位和潜在的药物标.

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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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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...
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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
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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...
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