Transcription factor AP-2 alpha (Activating enhancer binding Protein 2alpha), also known as TFAP2A, is a protein that in humans is encoded by the TFAP2A gene. [5]
Transcription factor AP-2 alpha (Activating enhancer binding Protein 2alpha), also known as TFAP2A, is a protein that in humans is encoded by the TFAP2A gene. [5]
Transcription factor AP-2 alpha is a 52-kD sequence-specific DNA-binding protein that enhances transcription of specific genes by binding to a GC-rich DNA sequence first identified in the cis-regulatory region of SV40 virus DNA and in cis-regulatory regions of a variety of cellular genes. [6]
The TFAP2-alpha gene was isolated and found to be retinoic acid-inducible in NT2 teratocarcinoma cells suggesting a potential role for AP-2 alpha in cellular differentiation. [7] [8] [9]
During embryonic development, AP-2 alpha is expressed in neural crest cells migrating from the cranial neural folds during neural tube closure, and is also expressed in ectoderm, parts of the central nervous system, limb buds, and mesonephric system suggesting that AP-2 alpha plays an important role in the determination and development of these tissues. [10] Cranial neural crest cells populate the developing face and provide patterning information for craniofacial morphogenesis and generate most of the skull bones and the cranial ganglia. [11]
AP-2 alpha knockout mice die perinatally with cranio-abdominoschisis and severe dysmorphogenesis of the face, skull, sensory organs, and cranial ganglia. [12] Homozygous knockout mice also have neural tube defects followed by craniofacial and body wall abnormalities. [13] In vivo gene delivery of AP-2 alpha suppressed spontaneous intestinal polyps in the Apc(Min/+) mouse. [14] AP-2 alpha also functions as a master regulator of multiple transcription factors in the mouse liver. [15]
In melanocytic cells TFAP2A gene expression may be regulated by MITF. [16]
Mutations in the TFAP2A gene cause Branchio-oculo-facial syndrome often with a midline cleft lip. [17] In a family with branchio-oculo-facial syndrome (BOFS), [18] a 3.2-Mb deletion at chromosome 6p24.3 was detected. [19] Sequencing of candidate genes in that region in 4 additional unrelated BOFS patients revealed 4 different de novo missense mutations in the exons 4 and 5 of the TFAP2A gene.
A disruption of an AP-2 alpha binding site in an IRF6 enhancer is associated with cleft lip. [20] Mutations in IRF6 gene cause Van der Woude syndrome (VWS) [21] that is a rare mendelian clefting autossomal dominant disorder with lower lip pits in 85% of affected individuals. [22] The remaining 15% of individuals with Van der Woude syndrome show only cleft lip and/or cleft palate (CL/P) and are clinically indistinguishable from the common non syndromic CL/P. NSCL/P occur in approximately 1/700 live births and is one of the most common form of congenital abnormalities. A previous association study between SNPs in and around IRF6 and NSCL/P have shown significant results in different populations [23] and was independently replicated. [24] [25] [26] [27]
A search of NSCL/P cases for potential regulatory elements for IRF6 gene was made aligning genomic sequences to a 500 Kb region encompassing IRF6 from 17 vertebrate species. Human sequence as reference and searched for multispecies conserved sequences (MCSs). Regions contained in introns 5’ and 3’ flanking IRF6 were screened by direct sequencing for potential causative variants in 184 NSCL/P cases. The rare allele of the SNP rs642961 showed a significant association with cleft lip cases. Analysis of transcription factor binding site analysis showed that the risk allele disrupt a binding site for AP-2 alpha. [20]
Mutations in the AP-2 alpha gene also cause branchio-oculo-facial syndrome, [19] which has overlapping features with Van der Woude syndrome such as orofacial clefting and occasional lip pits what make rs642961 a good candidate for an etiological variant. These findings show that IRF6 and AP-2 alpha are in the same developmental pathway and identify a variant in a regulatory region that contributes substantially to a common complex disorder.
TFAP2A has been shown to interact with:
Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 also known as EP300 or p300 is an enzyme that, in humans, is encoded by the EP300 gene. It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth.
Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.
Interferon regulatory factor 6 also known as IRF6 is a protein that in humans is encoded by the IRF6 gene.
Signal transducer and activator of transcription 1 (STAT1) is a transcription factor which in humans is encoded by the STAT1 gene. It is a member of the STAT protein family.
Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.
Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene. It is a member of the STAT protein family. This protein is critical to the biological response of type I interferons (IFNs). STAT2 sequence identity between mouse and human is only 68%.
Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.
Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.
Interferon regulatory factor 2 is a protein that in humans is encoded by the IRF2 gene.
Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription factors.
Interferon regulatory factor 1 is a protein that in humans is encoded by the IRF1 gene.
Interferon regulatory factor 9 is a protein that in humans is encoded by the IRF9 gene, previously known as ISGF3G.
Interferon regulatory factor 5 is a protein that in humans is encoded by the IRF5 gene. The IRF family is a group of transcription factors that are involved in signaling for virus responses in mammals along with regulation of certain cellular functions.
Interferon regulatory factor 8 (IRF8) also known as interferon consensus sequence-binding protein (ICSBP), is a protein that in humans is encoded by the IRF8 gene. IRF8 is a transcription factor that plays critical roles in the regulation of lineage commitment and in myeloid cell maturation including the decision for a common myeloid progenitor (CMP) to differentiate into a monocyte precursor cell.
Nuclear factor 1 C-type is a protein that in humans is encoded by the NFIC gene.
Cbp/p300-interacting transactivator 2 is a protein that in humans is encoded by the CITED2 gene.
Transcription factor AP-4 , also known as TFAP4, is a protein which in humans is encoded by the TFAP4 gene.
Transcription initiation factor TFIID subunit 4B is a protein that in humans is encoded by the TAF4B gene.
Transcription factor AP-2 beta also known as AP2-beta is a protein that in humans is encoded by the TFAP2B gene.
Transcription factor AP-2 gamma also known as AP2-gamma is a protein that in humans is encoded by the TFAP2C gene. AP2-gamma is a member of the activating protein 2 family of transcription factors.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.