Related Experiment Video
Updated: Aug 7, 2026
13:47
Enhanced Reduced Representation Bisulfite Sequencing for Assessment of DNA Methylation at Base Pair Resolution
Published on: February 24, 2015
Identification of methylation-sensitive human transcription factors using meSMiLE-seq
Antoni J Gralak1,2, Katerina Faltejskova3,4, Ally W H Yang5
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Nature Communications
|August 5, 2026
Summary
Researchers mapped DNA binding motifs for 74 new human transcription factors (TFs) using SMiLE-seq. They also developed meSMiLE-seq to analyze TF binding to methylated DNA, revealing new insights into epigenetic regulation.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- Transcription factors (TFs) regulate gene expression, but their DNA-binding specificities are often unknown.
- Understanding TF binding is crucial for deciphering gene regulation.
Purpose of the Study:
- To identify DNA-binding motifs for uncharacterized human TFs.
- To investigate the influence of DNA methylation on TF binding.
- To expand the human TF codebook and provide a platform for studying epigenetic effects on TF binding.
Main Methods:
- Selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq) was used to assay 284 TFs.
- Methylation-sensitive SMiLE-seq (meSMiLE-seq) was developed to simultaneously probe binding to methylated and unmethylated DNA.
- DNA-binding models were generated for identified TFs.
Main Results:
- 74 new DNA-binding motifs were discovered for human TFs.
- meSMiLE-seq identified DNA-binding models for 48 TFs, including known methylation-sensitive binders.
- 11 TFs showed preference for methylated DNA, while 13 avoided it.
- ZHX2 was identified as a putative Z-DNA binder.
Conclusions:
- The study significantly expands the catalog of human TF DNA-binding specificities.
- The developed meSMiLE-seq platform offers a quantitative method to assess how DNA modifications impact TF binding.
- This work provides valuable insights into the role of TFs and epigenetics in gene regulation.
