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Cited by 54Genomics and Chromatin DynamicsAcute Lymphoblastic Leukemia researchChromatin Remodeling and Cancer

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

Open access
Wang, Eric, Kawaoka, Shinpei, Roe, Jae-Seok, Shi, Junwei, Hohmann, Anja F, Xu, Yali, Bhagwat, Anand S, Suzuki, Yutaka +2 more·2015·eLife
DOI 10.7554/elife.06377PMC PMC4409649
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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.

AI snapshot

Written from the paper’s full text.

TL;DR

TRIM33 is identified as a lineage dependency in B cell neoplasms that prevents apoptosis by deactivating a single enhancer upstream of the pro-apoptotic gene Bim. In murine B-ALL, TRIM33 is recruited by PU.1 to two enhancers with exceptional PU.1 motif density, and deleting the Bim −117 enhancer renders TRIM33 dispensable for leukemia cell survival.

Key findings

  • A negative-selection RNAi screen of 1,126 shRNAs targeting 259 chromatin regulators in murine B-ALL identified 16 dependencies, with TRIM33 as a unique B-ALL requirement; TRIM33 knockdown caused apoptosis and reduced viability in B-ALL, 38B9, and several human B cell cancer lines, but had negligible effects on MLL-AF9/NrasG12D AML and Notch-mutant T-ALL.
  • ChIP-seq in B-ALL found the two strongest TRIM33 enrichment sites at 117 kb upstream of Bim and 35 kb upstream of Atp1b3; these regions were active enhancers (H3K27ac-positive, H3K4me3-negative) and contained high densities of PU.1 motifs (17 instances at Bim −117 and 14 at Atp1b3 −35).
  • PU.1 occupied Bim −117 and Atp1b3 −35 plus more than 2,600 other genomic sites; PU.1 knockdown reduced TRIM33 occupancy and H3K27ac at Bim −117, while TRIM33 knockdown increased PU.1 occupancy and H3K27ac there, indicating TRIM33 antagonizes PU.1-dependent enhancer activation.
  • Bim knockdown or CRISPR-Cas9 deletion of the 1.4 kb Bim −117 element rendered B-ALL cells completely resistant to TRIM33 shRNA-induced apoptosis; three independent homozygous-deletion clones did not require TRIM33 for viability.

Methods

  • Murine B-ALL cells (BCR-ABL plus Arf inactivation), 38B9, MLL-AF9/NrasG12D AML, and Notch-mutant T-ALL cells were used for negative-selection shRNA screens, competition-based viability assays, Annexin V/DAPI apoptosis assays, and double-shRNA experiments.
  • Genome-wide profiling included RNA-seq after TRIM33 knockdown and ChIP-seq for TRIM33, PU.1, H3K27ac, and H3K4me3; peaks were called with MACS, and motif analysis used FIMO/MEME with the JASPAR PU.1 motif MA0080.3.
  • In vivo studies used doxycycline-regulated TRIM33 shRNA transgenic mice crossed to ROSA26-rtTA-M2 mice, with flow cytometry of bone marrow and spleen; CRISPR-Cas9 with two sgRNAs flanking Bim −117 generated homozygous deletion clones.

Limitations

  • The paper states that short-term TRIM33 suppression caused a modest myeloid expansion and notes that Trim33−/− mice have been shown to develop chronic myelomonocytic leukemia, so long-term TRIM33 inhibition might have pro-tumorigenic effects in certain tissues.
  • The paper states that the role of AML-specific enhancers at Bim −66 kb in rendering TRIM33 dispensable in AML is speculative.
  • Evident from the text: the mechanistic work is primarily in murine B-ALL and murine cell lines, with human B cell cancer lines tested mainly for sensitivity to TRIM33 knockdown rather than for the Bim enhancer mechanism.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.7554/elife.06377

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

11 of 16 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured

  • Findingown data

    A v-Abl transformed B cell progenitor line, 38B9, and several human B cell cancer lines were sensitive to TRIM33 knockdown.

    “Furthermore, a v-Abl transformed B cell progenitor line, 38B9 (Alt et al., 1984), and several human B cell cancer lines were also sensitive to TRIM33 knockdown”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Alt et al., 1984 source
  • Premisecitation

    Trim33−/− mice have been shown to develop chronic myelomonocytic leukemia.

    “Trim33−/− mice have been shown to develop chronic myelomonocytic leukemia (Aucagne et al., 2011)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Aucagne et al., 2011 source

      The research article (p. 2) and Figure 3 (p. 4) report that Tif1g-deficient mice older than six months develop a CMML-like myeloproliferative disease. The claim captures the disease resemblance but omits the age qualifier and calls it CMML rather than CMML-like. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Findingown data

    Bim-deficient B-ALL cells were completely resistant to the apoptotic effects of TRIM33 shRNAs, indicating that Bim is the critical downstream repression target of TRIM33 to maintain cell viability.

    “Notably, Bim-deficient B-ALL cells were completely resistant to the apoptotic effects of TRIM33 shRNAs, indicating that Bim is the critical downstream repression target of TRIM33 to maintain cell viability”
    Quote in the paperSubstantial claim
  • Findingown data

    B cell production recovered fully in TRIM33-deficient mice upon restoring TRIM33 expression.

    “we found that B cell production recovered fully in TRIM33-deficient mice upon restoring TRIM33 expression”
    Quote in the paperSubstantial claim
  • Findingown data

    AML cells possess a large cluster of active enhancers located 66 kb upstream of Bim, which is not observed in B-ALL.

    “ChIP-seq analysis of H3K27ac revealed that AML cells possess a large cluster of active enhancers located 66 kb upstream of Bim, which is not observed in B-ALL”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 15
  • May combine two claims. 19

  • Classified as probably not a substantial claim.

    Premisecitation

    Bim encodes a BH3-only domain protein with a well-established pro-apoptotic function.

    “Bim encodes a BH3-only domain protein with a well-established pro-apoptotic function (Willis and Adams, 2005).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Willis and Adams, 2005 source

  • May combine two claims.

    Findingown data

    The level of H3K27ac is not skewed in a similar manner towards Bim -117 and Atp1b3 -35, indicating that these regions are not super-enhancers.

    “The level of the active enhancer chromatin mark, H3K27ac, is not skewed in a similar manner towards these two locations, indicating that these regions are not super-enhancers”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Hnisz et al., 2013 source

      The Results section, “Super-enhancers in many cell types” (page unavailable), supports using H3K27ac to identify super-enhancers. It does not report H3K27ac levels at Bim -117 or Atp1b3 -35, so it cannot verify the conclusion about those specific regions. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    The TRIM33-occupied regions upstream of Bim and Atp1b3 were enriched for H3K27 acetylation but not for H3K4 tri-methylation, suggesting that these elements are active enhancers.

    “The TRIM33-occupied regions upstream of Bim and Atp1b3 were enriched for H3K27 acetylation but not for H3K4 tri-methylation, suggesting that these elements are active enhancers”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Rada-Iglesias et al., 2011 source

      The paper describes H3K27ac enrichment with little or no H3K4me3 as part of the signature of putative active enhancers (Abstract; page unavailable). It does not report TRIM33 occupancy or measurements at regions upstream of Bim and Atp1b3, so it supports the interpretation of the marks but not the claim about those specific regions. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    TRIM33 was identified as a unique requirement in B-ALL, whereas the majority of other dependencies had been identified in a prior AML screen.

    “The majority of these factors had been identified in a prior screen that evaluated the requirement of chromatin regulators in MLL-AF9/NrasG12D acute myeloid leukemia (AML) (Zuber et al., 2011b), however TRIM33 was identified here as a unique requirement in B-ALL.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Zuber et al., 2011b source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    LSD1 suppresses thousands of enhancers in ES cells.

    “LSD1, a histone demethylase that has been shown previously to suppress active enhancers during embryonic stem (ES) cell differentiation (Whyte et al., 2012)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Whyte et al., 2012 source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Bim is upregulated as a means to eliminate auto-reactive B cells and to prevent autoimmune disease.

    “Bim is upregulated as a means to eliminate auto-reactive B cells and to prevent autoimmune disease”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Bouillet et al., 1999 source
    • cites Enders et al., 2003 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fluorescent markers eGFP (for shRenilla) and TurboGFP (for shTRIM33) indicate shRNA-expressing cells following doxycycline treatment.

    “Fluorescent markers (eGFP for shRenilla and TurboGFP for shTRIM33) were indicators of shRNA-expressing cells following doxycycline treatment.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Premsrirut et al., 2011 source

      The Results sections “Generation of a targeting construct” and “ColA1 targeted shRNAs enable potent and reversible knockdown in ES cells” describe doxycycline-inducible GFP as a visual reporter of shRNA expression. Our copy does not establish the specific assignments of eGFP to shRenilla or TurboGFP to shTRIM33. No page numbers are available in the indexed passages. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites Dow et al., 2012 source

      The Introduction (The basics of Col1a1-targeted shRNA transgenic mice; page unavailable) describes a fluorescent reporter linked to inducible shRNA expression, and the Procedure (Testing ES cell clones; page unavailable) uses GFP fluorescence to check induction after doxycycline treatment. Our copy does not establish the specific eGFP–shRenilla or TurboGFP–shTRIM33 pairings. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In humans, a reversible depletion of normal B cells is a well-tolerated side effect of the anti-CD20 antibody rituximab, which is an efficacious therapy in mature B cell neoplasms and in autoimmune disease.

    “In humans, a reversible depletion of normal B cells is a well-tolerated side effect of the anti-CD20 antibody rituximab, which is an efficacious therapy in mature B cell neoplasms and in autoimmune disease”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Coiffier et al., 2002 source
    • cites Edwards et al., 2004 source

      The Abstract (page unavailable) describes rituximab as an anti-CD20 antibody that causes transient B-cell depletion and is approved for certain CD20-positive B-cell lymphomas. The trial reports improved rheumatoid arthritis symptoms, while the adverse-events section finds similar overall adverse-event rates but notes serious infections and the need for longer-term monitoring. The claim extends efficacy from those specific conditions to mature B-cell neoplasms and autoimmune disease generally, and describes tolerability without those safety qualifications. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    PU.1 occupancy was confirmed at Bim -117 and Atp1b3 -35 in 38B9 and AML cells, but not in T-ALL.

    “Using ChIP-qPCR, we also confirmed PU.1 occupancy at these two regions in 38B9 and AML cells, but not in T-ALL”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    PU.1-deficient B-ALL cells harbored reduced H3K27ac at Bim -117 and reduced Bim mRNA levels, suggesting that PU.1 is responsible for maintaining this enhancer in an active state while also facilitating TRIM33 recruitment.

    “PU.1-deficient B-ALL cells also harbored reduced H3K27ac at Bim –117 and reduced Bim mRNA levels, suggesting that PU.1 is responsible for maintaining this enhancer in an active state while, paradoxically, also facilitating TRIM33 recruitment”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Knockdown of TRIM33 led to an increase in PU.1 occupancy and H3K27 acetylation at Bim -117, suggesting that TRIM33 antagonizes PU.1 binding to DNA and suppresses enhancer activity.

    “Interestingly, knockdown of TRIM33 led to an increase in PU.1 occupancy and H3K27 acetylation at Bim –117, suggesting that TRIM33 antagonizes PU.1 binding to DNA and suppresses enhancer activity”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kusy et al., 2011 source

  • May combine two claims.

    Findingown data

    Knockdown of TRIM33 in AML does not result in apoptosis or Bim upregulation.

    “knockdown of TRIM33 in AML does not result in apoptosis or Bim upregulation”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    TRIM33 knockdown led to negligible effects on the histological appearance of colon, liver, thymus, and pancreatic tissues and led to no significant changes in animal weight.

    “Notably, TRIM33 knockdown led to negligible effects on the histological appearance of colon, liver, thymus, and pancreatic tissues and led to no significant changes in animal weight”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Flow cytometry analysis of bone marrow and spleen following 1 or 4 weeks of dox administration revealed a selective loss of CD19+ and B220+ B lymphoid cells in TRIM33-deficient animals, while erythroid, myeloid, and T lymphoid populations remained intact or even increased in relative abundance.

    “Flow cytometry analysis of the bone marrow and spleen following 1 or 4 weeks of dox administration revealed a selective loss of CD19+ and B220+ B lymphoid cells in TRIM33-deficient animals, while erythroid, myeloid, and T lymphoid populations remained intact or even increased in relative abundance”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    TRIM33 occupancy was observed at the same two regions in 38B9, AML, and whole spleen, but not in T-ALL.

    “We also observed TRIM33 occupancy at these same two regions in 38B9, AML, and in whole spleen, but not in T-ALL”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Bim knockdown and the deletion of the Bim -117 region also rendered 38B9 cells resistant to the lethal effects of TRIM33 suppression.

    “Bim knockdown and the deletion of the Bim –117 region also rendered 38B9 cells resistant to the lethal effects of TRIM33 suppression”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    PU.1 ChIP-seq analysis in B-ALL confirmed its association with Bim -117 and Atp1b3 -35, as well as with more than 2600 other genomic sites.

    “ChIP-seq analysis of PU.1 in B-ALL confirmed its association with Bim –117 and Atp1b3 –35, as well as with more than 2600 other genomic sites”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In dox-treated shRen and shTRIM33 transgenic mice, the GFP percentage in total spleen was approximately 15%.

    “The GFP percentage in the total spleen was approximately 15% for shTRIM33 and shRen mice on dox.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In dox-treated shRen and shTRIM33 transgenic mice, the GFP percentage in total bone marrow was approximately 75%.

    “The GFP percentage in total bone marrow was approximately 75% on dox for shRen and shTRIM33 mice.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    TRIM33 is concentrated at a small number of sites in the B-ALL genome, with two of these regions correlating with a repressive effect on the expression of nearby Atp1b3 and Bim genes.

    “This analysis suggests that TRIM33 is concentrated at a small number of sites in the B-ALL genome, with two of these regions correlating with a repressive effect on the expression of nearby Atp1b3 and Bim genes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The other gene expression changes incurred upon TRIM33 knockdown did not correlate with its genomic occupancy, suggesting they might be an indirect effect of B-ALL cells initiating an apoptotic response.

    “The other gene expression changes incurred upon TRIM33 knockdown did not correlate with its genomic occupancy (data not shown), suggesting they might be an indirect effect of B-ALL cells initiating an apoptotic response.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    B lymphoid cells are uniquely sensitive to TRIM33 inhibition, implicating TRIM33 as a lineage dependency in cancers of B cell origin.

    “Collectively, these findings suggest that B lymphoid cells are uniquely sensitive to TRIM33 inhibition, thus implicating TRIM33 as a lineage dependency in cancers of B cell origin.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The −117 deletion of individual CRISPR clones was further verified by Sanger sequencing.

    “The −117 deletion of individual clones was further verified by Sanger sequencing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Renilla and Rpa3 control shRNAs were included with each 96 well plate as negative and positive controls, respectively.

    “Renilla and Rpa3 control shRNAs were included with each 96 well plate as negative and positive controls, respectively.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    If an shRNA was introduced into B-ALL cells with a day 2 GFP percentage below 5%, this sample was discarded from the screen.

    “If an shRNA was introduced into B-ALL cells with a day 2 GFP percentage below 5%, this sample was discarded from the screen.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other bromodomain modules (e.g., BRD4) have proven to be amenable to direct chemical inhibition.

    “other bromodomain modules (e.g., BRD4) have proven to be amenable to direct chemical inhibition”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Prinjha et al., 2012 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    The heterogeneity in GFP expression between total bone marrow and total spleen requires GFP gating to accurately define hematopoietic phenotypes using flow cytometry.

    “This heterogeneity in GFP expression in these different tissues requires GFP gating to accurately define hematopoietic phenotypes using flow cytometry.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    Other TFs are also likely to recruit TRIM33, such as TCF3/E2A.

    “Our ChIP-seq analysis of TRIM33 in myeloid, B lymphoid, and T lymphoid leukemias suggests that other TFs are also likely to recruit TRIM33, such as TCF3/E2A”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The three independent TRIM33 shRNAs revealed similar results.

    “The three independent TRIM33 shRNAs revealed similar results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Two independent biological replicates were performed for each ChIP-seq experiment.

    “Two independent biological replicates were performed for each ChIP-seq experiment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The binding interaction between TRIM33 and PU.1 is likely cooperative on motif-rich DNA elements, which would account for the biased accumulation of TRIM33 at enhancers harboring an exceptional PU.1 density.

    “This binding interaction is likely to be cooperative on motif-rich DNA elements, which would account for the biased accumulation of TRIM33 at enhancers harboring an exceptional PU.1 density.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    TRIM33 is a negative regulator of enhancer activity, reminiscent of LSD1.

    “The role of TRIM33 as a negative regulator of enhancer activity is reminiscent of LSD1”
    Quote in the paperNot a substantial claim
32 of 32

  • The paper relies on this without support.

    GFP expression is extinguished upon removing dox.

    “GFP expression is extinguished upon removing dox.”
1 of 1

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Authors
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.
Affiliations
  • Cold Spring Harbor Laboratory (US)
  • The University of Tokyo (JP)
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2015-04-28
Volume
4
Pages
e06377-e06377
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.06377
PMC
PMC4409649
OpenAlex
W2098764195
Semantic Scholar
cf1f8518c276fc41bdd8ec32e2cdc36ad87560b9
Cited by
54
References
47
Citations by year
2026: 3 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 4 · 2019: 8 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 2
FWCI
2.10
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Cancer Center (NCC) (Cold Spring Harbor Laboratory CA455087)
  • Alex's Lemonade Stand Foundation for Childhood Cancer (A award)
  • Burroughs Wellcome Fund (BWF) (Career award for medical scientist)
  • Japan Society for the Promotion of Science (JSPS) (postdoctoral fellowship)
  • SASS Foundation for Medical Research (postdoctoral fellowship)
  • National Cancer Institute (NCI) (NCI F30 CA186632)
  • Boehringer Ingelheim Fonds (BIF) (PhD fellowship)
  • V Foundation for Cancer Research
  • National Institutes of Health (NIH) (NCI RO1 CA174793)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
TRIM33, B-cell acute lymphoblastic leukemia, apoptosis, enhancers, building information modeling, PU.1, transcriptional cofactors, transcription factor binding motifs
MeSH terms
Bcl-2-Like Protein 11, Proto-Oncogene Protein Spi-1, Animals, B-Lymphocytes, Binding Sites, Cell Survival, Enhancer Elements, Genetic, Humans

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