| Title | Pluripotency transcription factors and Tet1/2 maintain Brd4-independent stem cell identity. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Finley LWS, Vardhana SA, Carey BW, Alonso-Curbelo D, Koche R, Chen Y, Wen D, King B, Radler MR, Rafii S, Lowe SW, C Allis D, Thompson CB |
| Journal | Nat Cell Biol |
| Volume | 20 |
| Issue | 5 |
| Pagination | 565-574 |
| Date Published | 2018 May |
| ISSN | 1476-4679 |
| Keywords | Acetylation, Animals, Binding Sites, Cell Differentiation, Cell Line, Cell Lineage, Cell Self Renewal, Chromatin, Chromatin Assembly and Disassembly, Dioxygenases, DNA-Binding Proteins, Female, Gene Expression Regulation, Developmental, Histones, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors, Male, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Inbred ICR, Mouse Embryonic Stem Cells, Nanog Homeobox Protein, Nuclear Proteins, Phenotype, Protein Binding, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Signal Transduction, STAT3 Transcription Factor, Transcription Factors |
| Abstract | <p>A robust network of transcription factors and an open chromatin landscape are hallmarks of the naive pluripotent state. Recently, the acetyllysine reader Brd4 has been implicated in stem cell maintenance, but the relative contribution of Brd4 to pluripotency remains unclear. Here, we show that Brd4 is dispensable for self-renewal and pluripotency of embryonic stem cells (ESCs). When maintained in their ground state, ESCs retain transcription factor binding and chromatin accessibility independent of Brd4 function or expression. In metastable ESCs, Brd4 independence can be achieved by increased expression of pluripotency transcription factors, including STAT3, Nanog or Klf4, so long as the DNA methylcytosine oxidases Tet1 and Tet2 are present. These data reveal that Brd4 is not essential for ESC self-renewal. Rather, the levels of pluripotency transcription factor abundance and Tet1/2 function determine the extent to which bromodomain recognition of protein acetylation contributes to the maintenance of gene expression and cell identity.</p> |
| DOI | 10.1038/s41556-018-0086-3 |
| Alternate Journal | Nat Cell Biol |
| PubMed ID | 29662175 |
| PubMed Central ID | PMC5937285 |
| Grant List | P30 CA008748 / CA / NCI NIH HHS / United States R01 GM129380 / GM / NIGMS NIH HHS / United States U54 OD020355 / OD / NIH HHS / United States |