Abstract：
:One critical event in reprogramming to pluripotency is erasure of the somatic transcriptional program of starting cells. Here, we present the proof of principle of a strategy for reprogramming to pluripotency facilitated by small molecules that interfere with the somatic transcriptional memory. We show that mild chemical targeting of the acetyllysine-binding pockets of the BET bromodomains, the transcriptional bookmarking domains, robustly enhances reprogramming. Furthermore, we show that chemical targeting of the transcriptional bookmarking BET bromodomains downregulates or turns off the expression of somatic genes in both naive and reprogramming fibroblasts. Chemical blocking of the BET bromodomains also results in loss of fibroblast morphology early in reprogramming. We therefore experimentally demonstrate that cell fate conversion can be achieved by chemically targeting the transcriptional bookmarking BET bromodomains responsible for transcriptional memory.
journal_name
Cell Repjournal_title
Cell reportsauthors
Shao Z,Yao C,Khodadadi-Jamayran A,Xu W,Townes TM,Crowley MR,Hu Kdoi
10.1016/j.celrep.2016.08.060subject
Has Abstractpub_date
2016-09-20 00:00:00pages
3138-3145issue
12issn
2211-1247pii
S2211-1247(16)31141-Xjournal_volume
16pub_type
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