| Residential College | false |
| Status | 已發表Published |
| Cooperation of TET dioxygenase and pioneer transcription factor FOXA2 in pancreatic endocrine cell differentiation | |
KE JIE ; XIE RUIYU 
| |
| 2022-01-15 | |
| Size of Audience | 250 |
| Type of Speaker | poster presentation |
| Abstract | Pioneer transcription factors, such as the FOXA family members, play critical roles in cell fate determination. Recent studies suggest that FOXA2 contributes to enhancer priming and chromatin remodeling during pancreatic lineage specification. However, the precise mechanism of FOXA2 regulating chromatin remodeling remains poorly understood. Using a stepwise differentiation system toward pancreatic endocrine, we show that FOXA2 is involved in TET-mediated DNA demethylation to induce chromatin remodeling and enhance the binding of lineage-specific transcription factors. TET deletion leads to unique hypermethylation at loci which display a remarkable enrichment for FOXA2 as well as a reduction in chromatin accessibility. Using co-immunoprecipitation, we identify a direct interaction between TET1 and FOXA2 in cells derived from hESCs. FOXA2 ChIP-seq compared wild-type with TET-deficient cells reveals that FOXA2 binding is unchanged at the definitive endoderm stage, but significantly altered at the pancreatic progenitor stage. We further find that regions with decreased FOXA2 binding upon TET deletion are less assessable and enriched with NERUOD1 compared to regions with increased FOXA2 binding, suggesting that TET-mediated hydroxymethylation is processed at a subset of FOXA2 target sites to influence chromatin remodeling and binding of lineage-specific transcription factors. We are currently in the process of generating FOXA2 knockout cells in a Flag-tagged TET1 knock-in hESC line to determine the changes in TET1 binding, DNA hydroxymethylation, and chromatin accessibility upon FOXA2 deletion. Our study will expand the regulatory function of FOXA2 in lineage specification and unveil the role of FOXA2 in TET1-mediated chromatin remodeling during pancreatic differentiation. |
| Conference Date | 2022-01-15 |
| Conference Place | The 1st International Guangdong-Hong Kong-Macau Greater Bay Area Conference in Translational Medicine & the 4th Macau Stem Cell Symposium, Macau |
| Document Type | Presentation |
| Collection | DEPARTMENT OF BIOMEDICAL SCIENCES |
| Corresponding Author | XIE RUIYU |
| Affiliation | Faculty of Health Sciences, University of Macau, Macau |
| Recommended Citation GB/T 7714 | KE JIE,XIE RUIYU. Cooperation of TET dioxygenase and pioneer transcription factor FOXA2 in pancreatic endocrine cell differentiation, 2022-01-15. |
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