CIITA Antibodies

MHC class II transactivator (CIITA)

Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter. No DNA binding of in vitro translated CIITA was detected.

May act in a coactivator-like fashion through protein-protein interactions by contacting factors binding to the proximal MHC class II promoter, to elements of the transcription machinery, or both. Alternatively it might activate HLA class II transcription by modifying proteins which bind to the MHC class II promoter.

Gene Information

Human
Gene Name:	CIITA
Uniprot:	P33076
Entrez:	4261

Family

Belongs to:
No superfamily

Alternative Names

C2TA; C2TAMHC class II transactivator type III; CIITAIV; class II, major histocompatibility complex, transactivator; MHC class II transactivator; MHC2TANLR family, acid domain containing; NLRA; nucleotide-binding oligomerization domain, leucine rich repeat and acid domaincontaining

Molecular Weight

Mass (kDA):
123.514 kDA

Genomic Context

Human
Location:	16p13.13
Sequence:	16; NC_000016.10 (10866208..10941562)

Subcellular Localizations

Nucleus. Nucleus, PML body. Recruited to PML body by PML.

Diseases

• Neoplasms
• Malignant Neoplasms
• Autoimmune Reaction
• Immunologic Deficiency Syndromes
• Inflammation
• Bare Lymphocyte Syndrome
• Severe Combined Immunodeficiency
• Melanoma
• Autoimmune Diseases
• Lymphoma
• Infective Disorder
• Carcinoma
• Congenital Combined Immunodeficiency

• Arthritis
• Leukemia
• Rheumatoid Arthritis
• Fibrosarcoma
• Malignant Paraganglionic Neoplasm
• Nervousness
• Tissue Adhesions

Interacting Proteins

• SIRT1
• ZXDA
• ZXDC

Pathways

• Immune Response
• Methylation
• Histone Acetylation
• Cell Activation
• Localization
• T Cell Activation
• Pathogenesis
• Cell Differentiation
• Dna Methylation
• Secretion
• Adaptive Immune Response
• Nuclear Export
• Nuclear Import

• Chromatin Remodeling
• Cell Death
• Antigen Processing And Presentation
• Phagocytosis
• Rna Interference
• Gene Silencing
• Inflammatory Response

PTMs

• Methylation
• Phosphorylation
• Acetylation
• Deacetylation
• Demethylation
• Ubiquitination

• Reduction
• Cleavage
• Prenylation
• Sumoylation
• Biotinylation
• Phosphorothioation

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/CIITA

Best Uses Of The CIITA Marker

This article examines how the CIITA marker influences MHC class II gene transcription. This is a key immunology target because it is expressed in a variety of antigen-presenting cell types. This article also discusses the relationship between CIITA (a gene that regulates MHC Class II gene expression) and RFX5. This article will explore the role of CIITA as a tumor as well as an autoimmune and inflammatory killer and its relationship with CIX5 or RFX5 genes.

CIITA regulates MHC class II gene expression

CIITA is an transcription factor that regulates expression of MHC class II genes. CIITA is not expressed in plasma B cells. Plasma B cells express CIITA through a protein called B-lymphocyte-induced maturity proteins-1 (Blimp-1) that interferes with the interaction between PU.1/IRF-4, and a consensus element of MHC class II genes.

CIITA acts as master regulator for MHC class II gene transcription, preventing the expression of this protein in cells that are not producing it. In cells that have constitutive MHC II gene expression, CIITA controls the expression of accessory proteins that are involved in presenting peptides correctly through MHC class II. Contrary to MHC II, CIITA does NOT directly communicate with DNA within its promoter region. Instead, it utilizes an enhanceosome subunit that contacts DNA and regulate the expression of MHC II genes.

CIITA acts as a central component of an enhanceosome. Unlike other transcription factors, it recruits CIITA to the enhanceosome, where it interacts with CREB and the NFY transactivator, and the RFX transcription factor. CIITA also recruits the canonical TFIID complex and replaces TAF1 in the promoter core.

CIITA is expressed in a variety of antigen-presenting cells.

CIITA is part of the C type lectin superfamily. It is expressed on numerous antigen-presenting cells such as monocytes and dendritic cells. CIITA expression is controlled by various regulatory factors in normal T cells. Specific transcription factors are required to activate CIITA promoters and trigger the expression of C-type lectins.

Bis are transcription factors that affect the phenotypes and function of certain autoimmune diseases. CIITA was found to be associated with three upstream transcriptional regulators predicted of B cells, monocytes naive, and T cells. This suggests that CIITA regulates the function of antigen-presenting cells. This study also identified novel CIITA target genes involved in autoimmune diseases.

CIITA targets a variety of non-MHC proteins. This gene complex was identified by chromatin immunoprecipitationas well as promoter arrays, and differential expression of genes in cell lines with no CIITA. CIITA binds to the MHC class II region as well as a major histone cluster at 6p21.3. 6p21.3. The results of these studies suggest that CIITA plays an ancillary function in the MHC class I region.

CIITA plays a role in the homeostasis of bone. CIITA plays a role in osteoclastogenesis as well being a regulator of MHC2 expression. Recent research has implicated CIITA in a variety of functions, like osteoclast differentiation and bone homeostasis. Its role in bone homeostasis is unknown.

CIITA is a novel target

CIITA, a newly recognized transcription factor could be a possible possibility for new drugs to fight cancer. Genetic mutations in this gene limit its ability to transactivate cells. Changes in the GBD or PCAF stimulate CIITA degrading and reduce its AT activity. PCAF also Acetylates the nuclear location N-terminal domain. This AT domain loss does not affect CIITA's transactivation activity.

Two distinct types of CIITA are encoded by the CIITA gene Type I and type 4. Human SMC CIITA type III and CIITA type IV are expressed in large quantities. But, when compared to the CIITA gene the pCAF gene is a carrier of an E3 ligase domain. CIITA co-expression with the pCAF gene results in the twofold increase in transactivity which is necessary for its function in driving MHC II transcription.

CIITA is expressed in high amounts in macrophages as well as dendritic cells, which are early targets of EBOV. CIITA overexpression in U2OS cell lines resulted in highly resistant phenotypes to native EBOV infection. The cells that were expressing CIITA showed lower expression of reporter genes Cell death and plaque formation were both decreased. CIITA did not affect the replication of EBOV minigenomes and this suggests that it does nothing to alter the viral replication complex.

While CIITA is not a brand new target in Boster Bio its potential to stimulate other genes is intriguing. CIITA can be utilized to target MHC class I gene transcription, and can also function as an important transcription factor to other genes in the body. However, the mechanism by which this enzyme functions will likely become more complex as more research is conducted. The capability of CIITA to activate other genes may depend on the nucleation sites that are upstream.

It is associated with CIITA

Multiple CIITA-enhanceosome-related interactions could have a reciprocal stabilization impact. Multiple interactions increase the binding of CIITA and promoter occupancy, and could account for some of the unproved observations. For example, CIITA can bind to the MHC II promoter only if it is expressed in vivo and requires the presence of RFX5. However, when CIITA is overexpressed, the expression of MHC-II is partially to be rescued.

A functional analysis has revealed that CIITA is closely linked to RFX5. Researchers discovered that RFX5 has a transcriptional "activation" domain through the use of GAL4 fusion proteins. Although this region isn't functional in all cells but it is essential for the transcriptional activity of. In vitro and in vivo, there was direct interaction between CIITA5 as well as RFX5 and this was confirmed by biochemical analysis using far-Western blot analysis.

The CIITA-RFX5 relationship extends previous research conducted using yeast two-hybrid systems. In order for RFX5's interaction with CIITA the amino acid stretch between residues 121-200 is essential. The CIITA-RFXANK/RFXB combo requires residues 1 to 335. These results indicate that one CIITA deletion mutation can result in a disruption in the interaction between CREB and CIITA.

The coimmunoprecipitation results in a weak association between CIITA and RFX in vitro. In contrast, CIITA is found to interact with multiple enhanceosome components, but the coimmunoprecipitation results are insufficient to detect interactions between the two. In addition, the overexpression of CIITA confirms that it interacts with various components of the enhanceosome.

CIITA BIs are located within 10 kb, or 150 Bp of a TSS

A genome-wide examination of CIITA markers data revealed that the majority of these BIs were not found within the MHC. They were mainly located in B cells. Only a few were discovered in monoocytes in naive state. 40 percent of the remaining BIs were linked to RFX5 binding, or were classified as CE markers and were located within 10 kb from the transcription start site. These results suggest that this marker could be used to identify potential new targets for drug development.

DNA-sequencing technology was used to examine this marker. We used the Stampy tool to align 51 bp-reads with the human genome. The data were then submitted to the Sequence Read Archive with the accession number PRJNA649987. The data was used to identify a subset of CIITA-expressing CD4+ cells in a tumor model.

Using CIITA DNA with DNA vaccines could improve their efficacy. The CIITA marker can trigger an enhanced E6-specific T-cell response which could lead to an antitumor-related therapeutic effect. It's also used to enhance the potency of DNA vaccines. Combining them with other DNA vaccines can enhance their effectiveness. The potential to improve the treatment of cancer is immense.

CIITA is an enzyme that is linked with MHC II. The MHC II transactivator CIITA promotes the expression of MHC II-related targets. Infection with Mtb increased the expression of Mpg-related targets including CIITA. These results are in agreement with previous studies on Mtb infection. The CIITA marker also increases IL-10, IL-12.

CIITA BIs are rich in genes involved in the immune response

CIITA is recognized for its ability to recruit enhanceosomes at the proximal promoter SXY sequences of classic MHC class II genes, but it also has the capacity to recruit distal enhancer elements, as evident by their sequence homology to the SXY module. The CIITA gene set is enriched for genes that are involved in the immune response, which includes autoimmune diseases and viral infections. The rs11074938 gene, one of the genes that are associated with the an increased amount of CIITA was detected in monocytes that had been isolated from fresh blood and B cells. This gene set was also associated with genes associated with cancer and autoimmune disorders.

The connection between CIITA gene expression and the characteristics of patients was discovered using a genetic map of 281 healthy volunteers. In this study we identified three enriching gene networks (BIs) and two non-MHC gene sets (CD74 and B2M). The study revealed biological themes linked to immune and inflammation. The most significantly enhanced pathway was the one that presented antigens, with rs11074938 in the 13th intron. The strongest link was trans associations with the HLA - DMA genes, the HLA-DRA genes.

If the gene is located within 10kb of its transcriptional starting point and is within 10 kb of its transcriptional start site, a CIITA BI can be linked with it. Sixty-three percent enriched BIs were associated with an individual gene and identified 442 genes. Moreover, CIITA BIs were associated with genes which have previously been identified as being involved in immune response. For example, CIITA gene expression is linked to the production of antibodies and the destruction of cancer cells.