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FLASH GENE
Symbol BCL6 contributors: mct/pgu - updated : 10-04-2016
HGNC name B-cell CLL/lymphoma 6
HGNC id 1001
DNA
TYPE functioning gene
STRUCTURE 24.31 kb     10 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   silencer
text structure
  • in the first intron, included in the region commonly deleted in B cell lymphoma
  • can be transcribed from alternative promoters, and there may be cell type-specific regulation and expression of these isoforms
  • promoter interacts with a distant upstream region, a 110-kb region, with a highly active histone modifications present only in normal Germinal center B cells and a GC B-cell line, overlapping with an alternative breakpoint region for chromosomal translocations and containing a GC-specific noncoding RNA gene
    • MAPPING cloned Y linked N status confirmed
    Map cen - PBE - KNG - HRG HRG /AHSG - D3S1262 - BCL6 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3575 78 706 - 2008 18675787
  • containing a different 5'UTR compared to variant 2 but encoding the same isoform
  • isoform 1
    • 10 - 3662 78 706 - 2008 18675787
  • isoform 1
    • 8 - 3086 - 650 - 2008 18675787
  • lacks exon 7 that encodes the first two zinc fingers
  • could form homodimers or heterodimers with BCL6 and could bind to classical BCL6-binding sites
  • compact repressor that may have a functional role in normal and neoplastic germinal center B cells
  • isoform 2
    		•
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node    
     tonsils    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell
    cell lineage B cells lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a BTB/POZ (zinc finger N-terminal) domain, encoded by sequence starting at exon 3
  • a PEST domain, the second repression domain (RDII) in the middle, interacts with the corepressor MTA3 (function of BCL6 may be modified by phosphorylation or acetylation of this domain)
  • six Krueppel-type (C2H2 type) C-terminal zinc finger motifs,
  • six C2H2-type ZFs encoded by exons 7 to 10, interacting with the corepressors NCOR1, NCOR2 and BCOR
    • HOMOLOGY
    interspecies homolog to murine Bcl6
    homolog to rattus LOC303836
    Homologene
    FAMILY
    CATEGORY regulatory , transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    text
  • BCL6 and FBXO11 co-localized in the nucleus where they showed overlapping, punctate staining throughout the nucleoplasm
    • basic FUNCTION
  • zinc finger transcriptional repressor or activator required for germinal center development and regulating B lymphocytes cell fate during the germinal center reaction by preventing terminal differentiation of B lymphocytes
  • supresses the expression of TP53 by binding two specific DNA sites in the p53 promoter region and modulates DNA damaged-induced apoptotic responses in germinal-centre B
  • recruiting a SMRT/SIN3A/histone deacetylase complex to mediate transcriptional repression
  • regulating gene expression to control inflammation, lymphocyte differentiation, and lymphomagenesis through repression of AP-1
  • transcriptional repressor, implicated in the pathogenesis of lymphomas, especially the diffuse large B-cell type
  • nuclear phosphoprotein that is the master regulator in germinal center (GC) formation and GC B-cell differentiation and survival
  • can also repress genes indirectly through binding to other transcription factors, such as peroxisome proliferator-activated receptor (PPARD and ZBTB17)
  • BCL6 and BCL6B regulate hematopoietic progenitor cells (HPC) homeostasis by an indirect pathway involving CD8 T cell
  • is required to prevent TP53-dependent apoptosis that results from hypermutation and chromosome rearrangement in germinal center B cells
  • having an important function in facilitating apoptosis of germinal center B cells via suppression of BCL2, and blocking this pathway may be critical for lymphomagenesis)
  • can suppress target gene expression by directly binding to specific DNA sequences or by interacting with PIAS2 or AP1 factors, which in turn bind DNA direct
  • required for programming of T follicular helper cell generation
  • transcriptional repressor that is essential for the germinal center (GC) reaction and important in lymphomagenesis
  • controls the transcription of a variety of genes involved in B-cell development, differentiation and activation
  • BCL6 and PIM1 are both protooncogenes that play roles in the pathogenesis of lymphoma
  • BCL6 protects senescent cells from accumulation of adenosine-targeted DNA mutations induced by ADAR
  • BCL6 and BACH2 cooperate to orchestrate gene expression patterning in germinal center (GC) B cells through both transcriptional and biochemical mechanisms, which collectively determine the proper initiation and timing of terminal differentiation
  • in addition to its well-recognized roles in immune regulation, BCL6 plays likely a role in regulatory events of lipid metabolism, and in the absence of BCL6, lipid metabolism in liver and adipose tissue is dysregulated
  • is a transcriptional repressor and critical mediator of the germinal center reaction during a T-cell-dependent antibody response
    • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling
    a component
  • PATZ1 and BCL6 form a complex in mammalian cells, and the POZ domain of PATZ1 is necessary for such interaction
  • complex comprising BCOR-BCL6-IRF8 modulates BCL6-associated transcriptional regulation of germinal center B cell function
  • BCL6-CUL3 complexes also provide essential negative feedback regulation during both thymocyte development and T cell activation to restrain excessive T follicular helper (Tfh) responses
    • INTERACTION
    DNA binding to the p53 promoter region
    RNA
    small molecule metal binding,
  • ion Zn2+ binding
    • protein
  • PDCD2
  • LRF binding
  • I3 SMRT/SIN3A/histone deacetylase complex binding
  • BTB-POZ transcriptional repressor constituting a potential therapeutic target for B cell lymphomas
  • interactions among BCL6, PDCD2, and other regulatory factors are likely to be very important in the development of B and T cell lymphomas
  • binds to the BCL2 promoter region by interacting with the transcriptional activator PIAS2 and suppresses PIAS2-induced activation of BCL2 expression)
  • transcriptional repressor of the POZ/BTB zinc-finger protein family, which binds to specific DNA sequences
  • interacting with PRDM1 (BCL6 and PRDM1 are powerful antagonistic master regulators of germinal center B cell differentiation and plasma cell differentiation)
  • interacting with BCOR through BTB domain despite the fact that BCOR has no detectable sequence similarity to the other two corepressors
  • interaction with PRL (inhibits BCL6 expression in breast cancer through a STAT5A-dependent mechanism)
  • targeted for ubiquitylation and proteasomal degradation by a SKP1–CUL1–F-box protein (SCF) ubiquitin ligase complex containing FBXO11
  • FBXO11 mediates the ubiquitylation and degradation of BCL6
  • PATZ1 interacts with BCL6 and negatively modulates its expression
  • CUL3 was also found associated with the BTB-ZF transcription factor BCL6, which directs the germinal-center B cell and follicular T-helper cell programs
  • HDAC4 may play an important role in suppressing cancers in conjunction with corepressors like BCL6 that recruit HDAC4 for repressing oncogenes
  • PRKAA2 exerts its anti-inflammatory effects through PARP1 and BCL6
  • likely HDAC1 functionally interacts with BCOR during eye development and, along with BCL6, act together to mediate normal optic cup formation by preventing colobomata
  • STAT3 increases expression of BCL6 and enhances recruitment of RNA polymerase II phosphorylated at a site associated with transcriptional initiation, but STAT5, represses BCL6 expression below basal levels and decreases the association of RNA polymerase II at the gene
  • BCL6-mediated transcriptional repression of LITAF may inhibit autophagy in B cells during the germinal centre reaction sorting
  • ZXDC is a regulator in the process of myeloid function and is responsible for CCL2 gene de-repression by BCL6
  • ZBTB33 is a key regulator of spleen germinal center formation by repressing BCL6 expression in splenocytes
  • BCL6 does not bind directly or indirectly to SLC22A6 promoter but increases the protein expression of HNF1A and thereby indirectly enhances SLC22A6 gene transcription
  • PELI1 directly interacted with the oncoprotein B cell chronic lymphocytic leukemia (BCL6) and induced lysine 63-mediated BCL6 polyubiquitination
  • activities of PIAS2 are altered by its interaction with the POZ-domain transcriptional repressors BCL6 and NACC1, and these interactions have been implicated in tumourigenesis in B-cell lymphomas and in ovarian serous carcinomas
  • BCL6 specifically binds to the interferon-regulatory factor IRF7 loci and restrains its transcription, thereby functioning as a negative regulator for interferon IFNB1 production and antiviral responses
  • IL4 and IL21 cooperate to induce the high BCL6 protein level required for germinal center formation
  • STAT3 and the Ikaros zinc finger transcription factors IKZF3, IKZF1 cooperate to regulate BCL66 expression
    • cell & other
    REGULATION
    repressed by binding of a repressive complex formed of ZEB1 and CTBP, to an E-box in the promoter
    Other regulated by PDCD2
    ASSOCIATED DISORDERS
    corresponding disease(s) FL3B
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    in B cell lymphomas, translocations t(3;14), t(3;13),t(2;3),t(3;22),t(3;4),t(3;11)and others
    tumoral fusion      
    in primary diffuse large B-cell lymphomas of the central nervous system with poor prognosis
    tumoral fusion      
    fused with histone H4 in t(3;6)(q27;p21), in non-Hodgkin's lymphoma
    tumoral   translocation    
    with HSPCA and GAPD in primary diffuse large B-cell lymphomas of the central nervous system
    tumoral   translocation    
    alternative translocation breakpoint cluster region associated with follicular lymphoma grade 3B
    tumoral somatic mutation      
    somatic point mutations in non-Hodgkin lymphomas (NHL)
    tumoral     --other  
    expressed in systemic anaplastic large cell lymphomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    combination modalities targeting the multiple oncogenic activities of BCL6 and the anti-apoptotic function of BCL2 may represent a rational approach for the treatment of a subset of DLBCL
    cancerhemopathy 
    dual targeting of oncogenic tyrosine kinases and BCL6-dependent feedback represents a novel strategy to eradicate drug-resistant and leukaemia-initiating subclones in tyrosine-kinase-driven leukaemia
    ANIMAL & CELL MODELS