In this episode of the Epigenetics Podcast, we caught up with Dr. Keji Zhao from the National Heart, Lung, and Blood Institute at the National Institutes of Health in Bethesda, MD, to talk about his work on the genome-wide investigation of epigenetic marks and nucleosome positioning.

Dr. Keji Zhao pioneered in the development of cutting-edge techniques in the field of epigenetics. Current methods at that time relied on DNA microarrays, however, Dr. Zhao wanted a more comprehensive and unbiased approach that would avoid the shortfalls of these array-based methods. Hence, he set out to develop new sequencing-based methods like ChIP-Seq and MNase-Seq with accompanying computational methods to analyze the huge amount of sequencing data that would be generated.

Using the above-mentioned techniques, Dr. Zhao was able to show that histone deacetylases (HDACs) and histone acetyltransferases (HATs) were found at inactive and active genes, respectively, as previously thought. Surprisingly, he was also able to show that HDACs were also located at active genes. Furthermore, both, HATs and HDACs can be found at low levels at silenced genes.

In this episode we discuss the story behind how Dr. Keji Zhao was one of the pioneers of the chromatin immunoprecipitation technology, how he discovered the genomic locations of HATs and HDACs, and in the end he shares some tips and tricks on how to get the best results in ChIP-Seq assays.



  • Artem Barski, Suresh Cuddapah, … Keji Zhao (2007) High-resolution profiling of histone methylations in the human genome (Cell) DOI: 10.1016/j.cell.2007.05.009
  • Dustin E. Schones, Kairong Cui, … Keji Zhao (2008) Dynamic regulation of nucleosome positioning in the human genome (Cell) DOI: 10.1016/j.cell.2008.02.022
  • Zhibin Wang, Chongzhi Zang, … Keji Zhao (2009) Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes (Cell) DOI: 10.1016/j.cell.2009.06.049
  • Wenfei Jin, Qingsong Tang, … Keji Zhao (2015) Genome-wide detection of DNase I hypersensitive sites in single cells and FFPE tissue samples (Nature) DOI: 10.1038/nature15740
  • Binbin Lai, Weiwu Gao, … Keji Zhao (2018) Principles of nucleosome organization revealed by single-cell micrococcal nuclease sequencing (Nature) DOI: 10.1038/s41586-018-0567-3

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