BCL6
Description
The BCL6 (BCL6 transcription repressor) is a protein-coding gene located on chromosome 3.
Bcl-6 (B-cell lymphoma 6) is a protein that in humans is encoded by the BCL6 gene. BCL6 is a master transcription factor for regulation of T follicular helper cells (TFH cells) proliferation. BCL6 has three evolutionary conserved structural domains. The interaction of these domains with corepressors allows for germinal center development and leads to B cell proliferation. The deletion of BCL6 is known to lead to failure of germinal center formation in the follicles of the lymph nodes, preventing B cells from undergoing somatic hypermutation. Mutations in BCL6 can lead to B cell lymphomas because it promotes unchecked B cell growth. Clinically, BCL6 can be used to diagnose B cell lymphomas and is shown to be upregulated in a number of cancers. Other BCL genes, including BCL2, BCL3, BCL5, BCL7A, BCL9, and BCL10, also have clinical significance in lymphoma.
== Normal physiological function ==
=== Structure === The protein encoded by the BCL6 gene is a zinc finger transcription factor that has three evolutionarily conserved domains. BCL6 contains a (1) N-terminal BTB/POZ domain (Broad-complex, Tramtrack and Brick-a-brac/Pox virus and Zin finger family domain), (2) a central RN2 region, and (3) another zinc finger at the C-terminal end.
BCL6 is a transcriptional repressor crucial for germinal center (GC) formation and antibody affinity maturation. Its mechanism of action varies depending on the cell lineage and biological function. BCL6 forms complexes with corepressors and histone deacetylases to repress the transcription of specific target genes. It can directly bind to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly suppress the activity of transcription factors. In GC B cells, BCL6 represses genes involved in differentiation, inflammation, apoptosis, and cell cycle control. It also autoregulates its own transcription and indirectly upregulates genes important for GC reactions, such as AICDA, by repressing microRNAs like miR155. A critical function of BCL6 is allowing GC B cells to proliferate rapidly in response to T cell-dependent antigens and tolerate DNA breaks required for immunoglobulin class switch recombination and somatic hypermutation without triggering p53/TP53-dependent apoptosis. In follicular helper CD4(+) T cells (T(FH) cells), BCL6 promotes the expression of T(FH)-related genes while inhibiting the differentiation of T(H)1, T(H)2, and T(H)17 cells. It also plays a role in establishing and maintaining immunological memory for both T and B cells. BCL6 suppresses macrophage proliferation by competing with STAT5 for binding motifs on target genes like CCL2 and CCND2. In response to genotoxic stress, BCL6 controls cell cycle arrest in GC B cells through both p53/TP53-dependent and -independent pathways. Additionally, BCL6 influences neurogenesis by altering the composition of NOTCH-dependent transcriptional complexes at specific NOTCH targets, such as HES5, which involves recruiting the deacetylase SIRT1, leading to epigenetic silencing and neuronal differentiation.
BCL6 is also known as BCL5, BCL6A, LAZ3, ZBTB27, ZNF51.
