| Autor: |
Rebecca Broome, Igor Chernukhin, Stacey Jamieson, Kamal Kishore, Evangelia K. Papachristou, Shi-Qing Mao, Carmen Gonzalez Tejedo, Areeb Mahtey, Vasiliki Theodorou, Arnoud J. Groen, Clive D’Santos, Shankar Balasubramanian, Anca Madalina Farcas, Rasmus Siersbæk, Jason S. Carroll |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 34, Iss 8, Pp 108776- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2021.108776 |
| Popis: |
Summary: Estrogen receptor-α (ER) drives tumor development in ER-positive (ER+) breast cancer. The transcription factor GATA3 has been closely linked to ER function, but its precise role in this setting remains unclear. Quantitative proteomics was used to assess changes to the ER complex in response to GATA3 depletion. Unexpectedly, few proteins were lost from the ER complex in the absence of GATA3, with the only major change being depletion of the dioxygenase TET2. TET2 binding constituted a near-total subset of ER binding in multiple breast cancer models, with loss of TET2 associated with reduced activation of proliferative pathways. TET2 knockdown did not appear to change global methylated cytosine (5mC) levels; however, oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) was significantly reduced, and these events occurred at ER enhancers. These findings implicate TET2 in the maintenance of 5hmC at ER sites, providing a potential mechanism for TET2-mediated regulation of ER target genes. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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