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The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer [RNA-Seq]

ABSTRACT: Most mammalian transcription factors 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 transcription factor. 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. RNA-Seq for shRNAs targeting Trim33 expressing B-ALL

ORGANISM(S): Mus musculus

SUBMITTER: Jae Seok Roe

PROVIDER: E-GEOD-66232 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer [ChIP-Seq]

Project description:Most mammalian transcription factors 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 transcription factor. 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. ChIP-Seq for Trim33, Pu.1 and histone modification marks in different types of leukemia cells

2015-04-06 | E-GEOD-66233 | biostudies-arrayexpress

The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer [RNA-Seq]

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Dynamics of TRIM33 binding in macrophages and effects of TRIM33 deletion on chromatin state during activation of primary macrophages.

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Interplay between FACT subunit SPT16 and TRIM33 can remodel chromatin at macrophage distal regulatory elements [ChIP-seq]

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TRIM33 switches off Ifnb1 transcription during the late phase of macrophage activation

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

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

| PRJNA276149 | ENA