Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of transcription factors. In GC B-cells, represses genes that function in differentiation, inflammation, apoptosis and cell cycle control, also autoregulates its transcriptional expression and up-regulates, indirectly, the expression of some genes important for GC reactions, such as AICDA, through the repression of microRNAs expression, like miR155. An important function is to allow GC B-cells to proliferate very rapidly in response to T-cell dependent antigens and tolerate the physiological DNA breaks required for immunglobulin class switch recombination and somatic hypermutation without inducing a p53/TP53-dependent apoptotic response. In follicular helper CD4(+) T-cells (T(FH) cells), promotes the expression of T(FH)-related genes but inhibits the differentiation of T(H)1, T(H)2 and T(H)17 cells. Also required for the establishment and maintenance of immunological memory for both T- and B-cells. Suppresses macrophage proliferation through competition with STAT5 for STAT-binding motifs binding on certain target genes, such as CCL2 and CCND2. In response to genotoxic stress, controls cell cycle arrest in GC B-cells in both p53/TP53-dependedent and -independent manners. Besides, also controls neurogenesis through the alteration of the composition of NOTCH-dependent transcriptional complexes at selective NOTCH targets, such as HES5, including the recruitment of the deacetylase SIRT1 and resulting in an epigenetic silencing leading to neuronal differentiation. Expressed in germinal center T- and B-cells and in primary immature dendritic cells. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: C2H2-type zinc finger protein; Oncoprotein; Transcription factor
Molecular Function: chromatin binding; chromatin DNA binding; DNA binding; DNA-binding transcription factor activity; DNA-binding transcription repressor activity, RNA polymerase II-specific; identical protein binding; intronic transcription regulatory region sequence-specific DNA binding; metal ion binding; nucleic acid binding; protein binding; RNA polymerase II regulatory region sequence-specific DNA binding; sequence-specific DNA binding
Biological Process: actin cytoskeleton organization; B cell differentiation; cell morphogenesis; cellular response to DNA damage stimulus; erythrocyte development; germinal center formation; immune system process; inflammatory response; negative regulation of apoptotic process; negative regulation of cell differentiation; negative regulation of cell growth; negative regulation of cell proliferation; negative regulation of cell-matrix adhesion; negative regulation of cellular senescence; negative regulation of isotype switching to IgE isotypes; negative regulation of mast cell cytokine production; negative regulation of Notch signaling pathway; negative regulation of Rho protein signal transduction; negative regulation of T-helper 2 cell differentiation; negative regulation of transcription by RNA polymerase II; negative regulation of transcription, DNA-templated; negative regulation of type 2 immune response; positive regulation of apoptotic process; positive regulation of B cell proliferation; positive regulation of cellular component movement; positive regulation of histone deacetylation; positive regulation of neuron differentiation; positive regulation of regulatory T cell differentiation; protein localization; regulation of cell proliferation; regulation of GTPase activity; regulation of inflammatory response; regulation of memory T cell differentiation; regulation of transcription by RNA polymerase II; Rho protein signal transduction; spermatogenesis; type 2 immune response