Novel sequence motif regulates pluripotency

Abstract

The pluripotency of embryonic stem cells (ESCs), combined with theoretically unlimited self-renewal characteristic, has greatly promoted the development of ESCs applying in regenerative medicine and organ transplantation fields. Deciphering the mechanisms of pluripotency would offer a much deeper understanding of the specific reprogramming process of ESCs. In our study, we tried to understand the networked regulations on the genomic level. Thanks to recently developed next-generation sequencing technologies, genome-wide maps of chromatin state has been established. The patterns of mammalian chromatin can offer insights into the locations and functions of underlying regulatory elements and genes. Here, we tried to recognize the specific regulatory sequence characteristics from the open chromatin signals on ES cells' genome. After obtaining ‘informative’ ESC-specific open chromatin (OC) bins, which were open chromatin sequences with length around 500 bp and expressed significantly higher in ESCs than other tissues, we applied MEME’s ‘discriminative motif discovery’ model to extract ESC-specific OC motifs. Then we filtered motifs that were conserved with each other and significantly more enriched in ESC OC bins compared with non-ESC OC bins. Around 60 sequence motifs were disclosed and we found that there is bias of nucleotide occurrence in some of the identified ESC open chromatin regions. This knowledge spreads us a much clearer image about the short and specific sites, which would introduce TF-DNA interactions in vivo and maintain pluripotent stability, on the human genome. Furthermore, such knowledge may also help us design novel functional elements that could be in response to the inside environmental signals in the pluripotent cells.