FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function.
Forkhead box A1 (FOXA1) is an FKHD family protein that plays pioneering roles in lineage-specific enhancer activation and gene transcription. Through genome-wide location analyses, here we show that FOXA1 expression and occupancy are, in turn, required for the maintenance of these epigenetic signatu...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2016
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| _version_ | 1797071787663556608 |
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| author | Yang, Y Zhao, J Fong, K Kim, J Li, S Song, C Song, B Zheng, B He, C Yu, J |
| author_facet | Yang, Y Zhao, J Fong, K Kim, J Li, S Song, C Song, B Zheng, B He, C Yu, J |
| author_sort | Yang, Y |
| collection | OXFORD |
| description | Forkhead box A1 (FOXA1) is an FKHD family protein that plays pioneering roles in lineage-specific enhancer activation and gene transcription. Through genome-wide location analyses, here we show that FOXA1 expression and occupancy are, in turn, required for the maintenance of these epigenetic signatures, namely DNA hypomethylation and histone 3 lysine 4 methylation. Mechanistically, this involves TET1, a 5-methylcytosine dioxygenase. We found that FOXA1 induces TET1 expression via direct binding to its cis-regulatory elements. Further, FOXA1 physically interacts with the TET1 protein through its CXXC domain. TET1 thus co-occupies FOXA1-dependent enhancers and mediates local DNA demethylation and concomitant histone 3 lysine 4 methylation, further potentiating FOXA1 recruitment. Consequently, FOXA1 binding events are markedly reduced following TET1 depletion. Together, our results suggest that FOXA1 is not only able to recognize but also remodel the epigenetic signatures at lineage-specific enhancers, which is mediated, at least in part, by a feed-forward regulatory loop between FOXA1 and TET1. |
| first_indexed | 2024-03-06T22:58:15Z |
| format | Journal article |
| id | oxford-uuid:612c1889-f782-4883-8a57-bb7ef511ae17 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:58:15Z |
| publishDate | 2016 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:612c1889-f782-4883-8a57-bb7ef511ae172022-03-26T17:58:03ZFOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:612c1889-f782-4883-8a57-bb7ef511ae17EnglishSymplectic Elements at OxfordOxford University Press2016Yang, YZhao, JFong, KKim, JLi, SSong, CSong, BZheng, BHe, CYu, JForkhead box A1 (FOXA1) is an FKHD family protein that plays pioneering roles in lineage-specific enhancer activation and gene transcription. Through genome-wide location analyses, here we show that FOXA1 expression and occupancy are, in turn, required for the maintenance of these epigenetic signatures, namely DNA hypomethylation and histone 3 lysine 4 methylation. Mechanistically, this involves TET1, a 5-methylcytosine dioxygenase. We found that FOXA1 induces TET1 expression via direct binding to its cis-regulatory elements. Further, FOXA1 physically interacts with the TET1 protein through its CXXC domain. TET1 thus co-occupies FOXA1-dependent enhancers and mediates local DNA demethylation and concomitant histone 3 lysine 4 methylation, further potentiating FOXA1 recruitment. Consequently, FOXA1 binding events are markedly reduced following TET1 depletion. Together, our results suggest that FOXA1 is not only able to recognize but also remodel the epigenetic signatures at lineage-specific enhancers, which is mediated, at least in part, by a feed-forward regulatory loop between FOXA1 and TET1. |
| spellingShingle | Yang, Y Zhao, J Fong, K Kim, J Li, S Song, C Song, B Zheng, B He, C Yu, J FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function. |
| title | FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function. |
| title_full | FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function. |
| title_fullStr | FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function. |
| title_full_unstemmed | FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function. |
| title_short | FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function. |
| title_sort | foxa1 potentiates lineage specific enhancer activation through modulating tet1 expression and function |
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