The process of somatic hypermutation (SHM) of immunoglobulin (Ig) genes requires activation-induced cytidine deaminase (AID). (northwestern.edu)
Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes. (uchicago.edu)
Class-switch recomb2
The Ig heavy chain locus super-enhancer is a very large (25kb) cis-regulatory region, including multiple enhancers and controlling several major modifications of the locus (notably somatic hypermutation, class-switch recombination and locus suicide recombination). (wikipedia.org)
Later in B cell development, usually after antigen-dependent activation of B cells, the genetic alteration processes of somatic mutation (SM), class switch recombination (CSR), and gene conversion further diversify the antigen-recognition repertoire as well as the effector function of encoded antibodies. (silverchair.com)
Processes of somatic1
In the GC, the combined processes of somatic hypermutation and selection based on the affinity of the BCR for the antigen, are responsible for the generation of high-affinity antibody variants which ultimately differentiate into long-lived plasma cells or long-lived memory B cells. (osaka-u.ac.jp)
Genes18
In genetics, a super-enhancer is a region of the mammalian genome comprising multiple enhancers that is collectively bound by an array of transcription factor proteins to drive transcription of genes involved in cell identity. (wikipedia.org)
Because super-enhancers are frequently identified near genes important for controlling and defining cell identity, they may thus be used to quickly identify key nodes regulating cell identity. (wikipedia.org)
Super-enhancers are bound by higher levels of transcription-regulating proteins and are associated with genes that are more highly expressed. (wikipedia.org)
Expression of genes associated with super-enhancers is particularly sensitive to perturbations, which may facilitate cell state transitions or explain sensitivity of super-enhancer-associated genes to small molecules that target transcription. (wikipedia.org)
In 2013, two labs identified large enhancers near several genes especially important for establishing cell identities. (wikipedia.org)
Both super-enhancers and stretch enhancers are clusters of enhancers that control cell-specific genes and may be largely synonymous. (wikipedia.org)
These particularly large, potent enhancer regions were found to control the genes that establish the embryonic stem cell identity, including Oct-4, Sox2, Nanog, Klf4, and Esrrb. (wikipedia.org)
Perturbation of the super-enhancers associated with these genes showed a range of effects on their target genes' expression. (wikipedia.org)
The enhancers comprising super-enhancers share the functions of enhancers, including binding transcription factor proteins, looping to target genes, and activating transcription. (wikipedia.org)
Perturbing the DNA of enhancers comprising super-enhancers showed a range of effects on the expression of cell identity genes, suggesting a complex relationship between the constituent enhancers. (wikipedia.org)
However, housekeeping genes tend to be more highly expressed than super-enhancer-associated genes. (wikipedia.org)
Super-enhancers may have evolved at key cell identity genes to render the transcription of these genes responsive to an array of external cues. (wikipedia.org)
The constituent enhancers of super-enhancers physically interact with each other and their target genes over a long range sequence-wise. (wikipedia.org)
Ig genes are the most highly mutated genes, presumably because of multiple CAGGTG motifs within the Ig genes, high transcription activity, and the presence of other cooperating elements in Ig enhancers. (northwestern.edu)
B lymphocytes of xeroderma pigmentosum or Cockayne syndrome patients with inherited defects in nucleotide excision repair are fully capable of somatic hypermutation of immunoglobulin genes. (uchicago.edu)
Association of two different repetitive DNA elements near immunoglobulin light chain genes. (uchicago.edu)
B lymphocytes can produce an unlimited number of different antibodies against a diverse array of foreign bodies by utilizing random rearrangement of gene segments encoding antibodies (immunoglobulin genes). (osaka-u.ac.jp)
Mutation1
Epstein-Barr virus (EBV) infection, malaria, immunodeficiency and spontaneous, somatic mutation can all contribute to the origin and maintenance of this cancer and their mechanisms are the subject of this review. (bmj.com)
Locus1
A novel enhancer in the immunoglobulin lambda locus is duplicated and functionally independent of NF kappa B. (uchicago.edu)
Misalignment of V and J gene segments resulting in a nonfunctional immunoglobulin gene. (uchicago.edu)
Patterns1
Analyses of somatic hypermutation (SHM) patterns in B cell Ig sequences have important basic science and clinical applications, but they are often confounded by the intrinsic biases of SHM targeting on specific DNA motifs (i.e., hot and cold spots). (aai.org)
Proteins1
Three notable traits of enhancers comprising super-enhancers are their clustering in genomic proximity, their exceptional signal of transcription-regulating proteins, and their high frequency of physical interaction with each other. (wikipedia.org)
Sequences1
Immunoglobulin mu- and gamma-ribonucleic acid sequences in thymocytes and splenocytes from normal and hyperimmune mice. (uchicago.edu)
Reaction1
However, the tumour cells have undergone hypermutation, 21 23 a feature of the GC reaction during B-cell activation and differentiation. (bmj.com)
Heavy chain1
Immunoglobulin heavy-chain variable (IGHV) mutational status and trisomy 12 were most impactful on the CLL proteome. (bvsalud.org)
Region1
26 27 In contrast, the chromosomal breakpoint in sBL and HIV-associated BL occurs most commonly in the class switch region, 28 but since both somatic hypermutation and class switching are events that are normally confined to GC B cells and GC centroblast markers are expressed on BL cells, the BL progenitor cells most likely arise from B cells subjected to chromosomal rearrangements in the GC. (bmj.com)
Elements3
More recent research has suggested that these different categories of regulatory elements may represent subtypes of super-enhancer. (wikipedia.org)
We show that three CAGGTG cis-elements in the context of Ig enhancers are sufficient to target SHM to a nearby transcribed gene. (northwestern.edu)
The other cis-elements of Ig enhancers alone cannot attract the SHM machinery. (northwestern.edu)
Light chain1
The hallmark of all BL tumours is the translocation between the MYC gene and one of the immunoglobulin (Ig) heavy or light chain loci. (bmj.com)
Cells3
As currently defined, the term "super-enhancer" was introduced by Young's lab to describe regions identified in mouse embryonic stem cells (ESCs). (wikipedia.org)
Super-enhancers separated by tens of megabases cluster in three-dimensions inside the nucleus of mouse embryonic stem cells. (wikipedia.org)
They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. (lookformedical.com)
Cell1
Super-enhancers that control the expression of major cell surface receptors with a crucial role in the function of a given cell lineage have also been defined. (wikipedia.org)