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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
Corresponding disease
FL3B follicular lymphoma grade 3B
Location 3q27.3      Physical location : 187.439.164 - 187.463.513
Synonym name
  • zinc finger protein 51
  • lymphoma-associated zinc finger gene on chromosome 3
  • LAZ-3 protein
  • cys-his2 zinc finger transcription factor
    • Synonym symbol(s) LAZ3, BCL5, ZNF51, BCL6A, ZBTB27, BCL5A,
    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