Epigenetic remodeling of chromatin to promote pluripotent reprogramming— SUSTech-GIBH groups discover epigenetic roadblock Chris Edwards | 03/20/2018 177


In 2006, the Japanese researcher Shinya Yamanaka reported the Nobel prize winning breakthrough demonstrating that adult somatic cells could be converted back to an early embryonic state in a process termed ‘reprogramming’. This reprogramming process could be performed by artificially expressing just four DNA binding transcription factors, OCT4, SOX2, KLF4 and c-MYC, and these factors would comprehensively alter the adult somatic cell and convert it back to a pluripotent stem cell.

Since then researchers have worked hard to understand the reprogramming mechanism. During reprogramming, almost all aspects of the adult somatic cell change, and the cell fate is drastically altered in a complex series of biological processes that eventually results in the complete reprogramming to a pluripotent state. Despite over a decade of research the exact molecular principles governing reprogramming by OCT4, SOX2, KLF4 and c-MYC still remain somewhat mysterious.

New research, led by first authors Zhuang Qiang, Li Wenjuan and Christine Benda, in a multi-research institute team, show that NCoR and SMRT recruit the histone deacetylase HDAC3 to release epigenetic blocks stopping the conversion of cells back to a pluripotent state. In a process mainly driven by c-MYC, the co-repressor complex works to deacetylate histones, block gene expression, and so block reprogramming. Removing NCoR/SMRT relieves this block, and allows the cells to reprogram more rapidly and efficiently. This work reveals new insights into the epigenetic control of the reprogramming process, and the chromatin modifications that are required for successful reprogramming. 

This work was jointly led by Andrew Hutchins, an Assistant Professor at SUSTech and Miguel Esteban, a Professor at the Guangzhou Institutes of Biomedicine and Health (Chinese Academy of Sciences). The study was published in the leading journal Nature Cell Biology, and is titled: “NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming”. 

Link: http://dx.doi.org/10.1038/s41556-018-0047-x