The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer

Wang, E., Kawaoka, S., Roe, J. S., Shi, J., Hohmann, A. F., Xu, Y., Bhagwat, A. S., Suzuki, Y., Kinney, J. B., Vakoc, C. R. (April 2015) The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer. Elife, 4. ISSN 2050-084X (Electronic)2050-084X (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/25919951
DOI: 10.7554/eLife.06377

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: B cell Bim Pu.1 Trim33 chromosomes enhancer genes human leukemia mouse
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
diseases & disorders > cancer > cancer types > leukemia
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service
CSHL labs > Kinney lab
CSHL labs > Vakoc lab
Watson School > Publications
Depositing User: Matt Covey
Date: 28 April 2015
Date Deposited: 30 Apr 2015 15:02
Last Modified: 03 Nov 2017 18:49
PMCID: PMC4409649
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31360

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