دورية أكاديمية
The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer
| العنوان: | The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer |
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| المؤلفون: | Eric Wang, Shinpei Kawaoka, Jae-Seok Roe, Junwei Shi, Anja F Hohmann, Yali Xu, Anand S Bhagwat, Yutaka Suzuki, Justin B Kinney, Christopher R Vakoc |
| المصدر: | eLife, Vol 4 (2015) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2015. |
| سنة النشر: | 2015 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | Trim33, enhancer, leukemia, PU.1, B cell, Bim, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Most mammalian transcription factors (TFs) and cofactors occupy thousands of genomic sites and modulate the expression of large gene networks to implement their biological functions. In this study, we describe an exception to this paradigm. TRIM33 is identified here as a lineage dependency in B cell neoplasms and is shown to perform this essential function by associating with a single cis element. ChIP-seq analysis of TRIM33 in murine B cell leukemia revealed a preferential association with two lineage-specific enhancers that harbor an exceptional density of motifs recognized by the PU.1 TF. TRIM33 is recruited to these elements by PU.1, yet acts to antagonize PU.1 function. One of the PU.1/TRIM33 co-occupied enhancers is upstream of the pro-apoptotic gene Bim, and deleting this enhancer renders TRIM33 dispensable for leukemia cell survival. These findings reveal an essential role for TRIM33 in preventing apoptosis in B lymphoblastic leukemia by interfering with enhancer-mediated Bim activation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/06377Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.06377 |
| الوصول الحر: | https://doaj.org/article/27863118c8f1495d93f82f9e13abfd0cTest |
| رقم الانضمام: | edsdoj.27863118c8f1495d93f82f9e13abfd0c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.06377 |