TEA consensus sequence gene transcriptions
"The TEA/ATTS transcription factor family consists of mammalian, avian, nematode, insect and fungal members that share a conserved TEA domain. The TEA domain represents a DNAbinding region that is composed of 6676 conserved amino acids (aa) in the Nterminal section of the proteins."

# Human genes

# Gene expressions

## TEAD1
Transcriptional enhancer factor TEF-1 also known as TEA domain family member 1 (TEAD1) and transcription factor 13 (TCF-13) is a protein that in humans is encoded by the TEAD1 gene. TEAD1 was the first member of the TEAD family of transcription factors to be identified.
All members of the TEAD family share a highly conserved DNA binding domain called the TEA domain. This DNA binding domain has a consensus DNA sequence 5-CATTCCA/T-3 that is called the MCAT element. The three dimensional structure of the TEA domain has been identified . Its conformation is close to that of the homeodomain and contains 3  helixes (H1, H2 and H3). It is the H3 helix that enables TEAD proteins to bind DNA.
Another conserved domain of TEAD1 is located at the C terminus of the protein. It allows the binding of cofactors and has been called the YAP1 binding domain, because it is its ability to bind this well-known TEAD proteins co-factor that led to its identification. Indeed, TEAD proteins cannot induce gene expression on their own. They have to associate with cofactors to be able to act
TEAD1 is expressed in various tissues including skeletal muscle, pancreas, placenta, lung, and heart.

## TEAD2
TEAD2 (ETF, ETEF-1, TEF-4), together with TEAD1, defines a novel family of transcription factors, the TEAD family, highly conserved through evolution. 
TEAD proteins were notably found in Drosophila (Scalloped), C. elegans (egl -44), S. cerevisiae and A. nidulans. 
TEAD2 has been less studied than TEAD1 but a few studies revealed its role during development.
TEAD2 is a member of the mammalian TEAD transcription factor family (initially named the transcriptional enhancer factor (TEF) family), which contain the TEA/ATTS DNA-binding domain. Members of the family in mammals are TEAD1, TEAD2, TEAD3, TEAD4.
TEAD2 is selectively expressed in a subset of embryonic tissues including the cerebellum, testis, and distal portions of the forelimb and hindlimb buds, as well as the tail bud, but it is essentially absent from adult tissues. TEAD2 has also been shown to be expressed very early during development, i.e. from the 2-cell stage.

## TEAD3
Transcriptional enhancer factor TEF-5 is a protein that in humans is encoded by the TEAD3 gene.
This gene product is a member of the transcriptional enhancer factor (TEF) family of transcription factors, which contain the TEA/ATTS DNA-binding domain. Members of the family in mammals are TEAD1, TEAD2, TEAD3, TEAD4. Transcriptional coregulators, such as WWTR1 (TAZ) bind to these transcription factors. TEAD3 is predominantly expressed in the placenta and is involved in the transactivation of the chorionic somatomammotropin-B gene enhancer. It is expressed in nervous system and muscle in fish embryos. Translation of this protein is initiated at a non-AUG (AUA) start codon.

## TEAD4
Transcriptional enhancer factor TEF-3 is a protein that in humans is encoded by the TEAD4 gene.
This gene product is a member of the transcriptional enhancer factor (TEF) family of transcription factors, which contain the TEA/ATTS DNA-binding domain. Members of the family in mammals are TEAD1, TEAD2, TEAD3, TEAD4. TEAD4 is preferentially expressed in the skeletal muscle, and binds to the M-CAT regulatory element found in promoters of muscle-specific genes to direct their gene expression. Alternatively spliced transcripts encoding distinct isoforms, some of which are translated through the use of a non-AUG (UUG) initiation codon, have been described for this gene. Gene ablation experiments in mice (i.e. knockout mice) showed that TEAD4 is essential for the formation of blastocysts during preimplantation embryo development. Although it was originally hypothesized to be essential for specification of trophectoderm lineage, it was later shown that functional trophectoderm can be produced leading to formation of blastocysts under in vitro conditions that suppress oxidative stress. Transcriptional coregulators, such as WWTR1 (TAZ) bind to members in this transcription factor family.

# TEAD Post-transcriptional modifications
Protein Kinase A (pKA) can phosphorylate TEAD1 at serine 102, after the TEA domain. This phosphorylation is needed for the transcriptional activation of the  MyHC gene. Protein Kinase C (pKC) phosphorylates TEAD1 on serine and threonine next to the last alpha loop in the TEA domain. This phosphorylation decreases TEAD1 binding to the GTIIC enhancer.
TEAD1 can be palmitoylated on a conserved cysteine at the C-term of the protein. This post-translational modification is critical for proper folding of TEAD proteins and their stability.

# TEAD Orthologs
TEAD proteins are found in many organisms under different names, assuming different functions.
For example, in Saccharomyces cerevisiae TEC-1 regulates the transposable element TY1 and is involved in pseudohyphale growth (the elongated shape that yeasts take when grown in nutrient-poor conditions).
In Aspergillus nidulans, the TEA domain protein ABAA regulates the differentiation of conidiophores.
In drosophila the transcription factor Scalloped is involved in the development of the wing disc, survival and cell growth.
In Xenopus laevis it has been demonstrated that the ortholog of TEAD1 regulates muscle differentiation.

# TEAD Functions
- Heart development (myocardium differentiation,
- Skeletal muscle development (alpha-actin of skeletal muscles),)
- Smooth muscle development (alpha-actin of smooth muscles),
- Regulation of myosin heavy chain genes, cardiac muscular genes troponin T and I 
- Regulation of proliferation,
- Regulation of apoptosis,
- Regulation of mouse neural development
- Neuron proliferation
- Regulation of proliferation
- Regulation of apoptosis

# TEAD Cofactors
TEAD proteins require cofactors to induce the transcription of target genes.

# TEAD interactions
TEAD1 interacts with all members of the SRC family of steroid receptor coactivators. In HeLa cells TEAD1 and SRC induce gene expression, TEAD1 interacts with PARP (Poly-ADP ribose polymerase) to regulate smooth muscle -actin expression. PARP can also ADP-ribosylate the TEAD proteins and make the chromatin context favorable to transcription through histone modification, SRF (Serum response factor) and TEAD1 together regulate gene expression.
TEAD proteins and MEF2 (myocyte enhancer factor 2) interact physically. The binding of MEF2 on DNA induces and potentiates TEAD1 recruitment at MCAT sequences that are adjacent to MEF2 binding sites. This recruitment leads to the repression of the MLC2v (Myosin Light Chain 2 v) and MHC ( -myosin heavy chain ) promoter. TEAD1 and the phosphoprotein MAX interact in vivo and in vitro. Once this complex is formed, these two proteins can regulate the alpha-myosin heavy chain (-MHC) gene expression.
The four Vestigial-like (VGLL) proteins are able to interact with all TEADs. The precise function of TEAD and VGLL interaction is still poorly understood. It has been shown that TEAD/VGLL1 complexes promote anchorage-independent cell proliferation in prostate cancer cell lines suggesting a role in cancer progression Moreover, VGLL2 interaction with TEAD1 activates muscle promoter upon C2C12 differentiation and enhances MyoD-mediated myogenic in 10T1/2. Finally the complex TEAD/VGLL4 acts as a default transcriptional repressor.
The interaction between YAP (Yes Associated Protein 65), TAZ, a transcriptional coactivator paralog to YAP, and all TEAD proteins was demonstrated both in vitro and in vivo. In both cases the interaction of the proteins leads to increased TEAD transcriptional activity. YAP/TAZ are effectors of the Hippo tumor suppressor pathway that restricts organ growth by keeping in check cell proliferation and promoting apoptosis in mammals and also in Drosophila.

# Cancers
Analysis of cancer transcriptome databases (www.ebi.ac.uk/gxa) showed that TEAD1 is dysregulated in several types of cancers. First in Kaposi sarcoma there is a 300-fold increase in TEAD1 levels. Moreover, the increase of TEAD expression can be detected in basal-like breast cancers, fallopian tube carcinoma, and germ cell tumors. Otherwise, in other types of cancer TEAD expression is decreased, for example in other breast cancer types and in renal or bladder cancers. This dual role can be explained by the different targets and the differential regulation of target genes by TEAD transcription factors. Finally recent studies showed that TEAD1 and YAP in ovarian cancer can induces cell stemness and chemoresistance. and that genetic variant of TEAD protein and YAP are enriched in some cancers.
Recent animal models indicating a possible association of TEAD2 with anencephaly.

# Consensus sequences
"The TEA consensus sequence (TCS) in a fungal TEA/ATTS transcription factor target promoter has been defined as 5CATTCY3 (Andrianopoulos and Timberlake, 1994)."

# Binding site for

# Enhancer activity

# Promoter occurrences

# Hypotheses
- A1BG has no regulatory elements in either promoter.
- A1BG is not transcribed by a regulatory element.
- No regulatory element participates in the transcription of A1BG.

# TEA samplings
Copying a responsive elements consensus sequence CATTC(C/T) and putting the sequence in "F" finds three between ZNF497 and A1BG or 2 between ZSCAN22 and A1BG as can be found by the computer programs.
For the Basic programs testing consensus sequence CATTC(C/T) (starting with SuccessablesTEA.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:
- negative strand, negative direction, looking for CATTC(C/T), 2, CATTCT at 3893, CATTCT at 2503.
- positive strand, negative direction, looking for CATTC(C/T), 0.
- positive strand, positive direction, looking for CATTC(C/T), 1, CATTCC at 2457.
- negative strand, positive direction, looking for CATTC(C/T), 2, CATTCT at 3074, CATTCC at 2208.
- inverse complement, negative strand, negative direction, looking for (A/G)GAATG, 0.
- inverse complement, positive strand, negative direction, looking for (A/G)GAATG, 3, GGAATG at 4554, AGAATG at 3003, AGAATG at 1947.
- inverse complement, positive strand, positive direction, looking for (A/G)GAATG, 2, AGAATG at 1887, AGAATG at 523.
- inverse complement, negative strand, positive direction, looking for (A/G)GAATG, 8, AGAATG at 3834, GGAATG at 3566, GGAATG at 3440, GGAATG at 3366, AGAATG at 3068, AGAATG at 2840, AGAATG at 1419, AGAATG at 1319.

## TEA (4560-2846) UTRs
- Negative strand, negative direction: CATTCT at 3893.
- Positive strand, negative direction: GGAATG at 4554, AGAATG at 3003.

## TEA negative direction (2596-1) distal promoters
- Negative strand, negative direction: CATTCT at 2503.
- Positive strand, negative direction: AGAATG at 1947.

## TEA positive direction (4050-1) distal promoters
- Negative strand, positive direction: CATTCT at 3074, CATTCC at 2208.
- Negative strand, positive direction: AGAATG at 3834, GGAATG at 3566, GGAATG at 3440, GGAATG at 3366, AGAATG at 3068, AGAATG at 2840, AGAATG at 1419, AGAATG at 1319.
- Positive strand, positive direction: CATTCC at 2457.
- Positive strand, positive direction: AGAATG at 1887, AGAATG at 523.

# TEA random dataset samplings
- TEAr0: 4, CATTCC at 3390, CATTCC at 3050, CATTCT at 1267, CATTCT at 891.
- TEAr1: 3, CATTCT at 2295, CATTCT at 1318, CATTCC at 774.
- TEAr2: 2, CATTCT at 1638, CATTCC at 116.
- TEAr3: 5, CATTCC at 3472, CATTCC at 3088, CATTCC at 2348, CATTCC at 1461, CATTCC at 481.
- TEAr4: 4, CATTCC at 3700, CATTCC at 2113, CATTCC at 1552, CATTCT at 310.
- TEAr5: 1, CATTCC at 3823.
- TEAr6: 3, CATTCT at 3999, CATTCC at 3690, CATTCC at 984.
- TEAr7: 3, CATTCT at 2272, CATTCT at 1946, CATTCT at 1018.
- TEAr8: 1, CATTCT at 1281.
- TEAr9: 2, CATTCC at 3660, CATTCT at 3103.
- TEAr0ci: 2, GGAATG at 1897, AGAATG at 934.
- TEAr1ci: 1, AGAATG at 2269.
- TEAr2ci: 2, GGAATG at 4492, GGAATG at 4356.
- TEAr3ci: 1, AGAATG at 4316.
- TEAr4ci: 2, GGAATG at 2701, AGAATG at 1100.
- TEAr5ci: 5, AGAATG at 4340, AGAATG at 3530, GGAATG at 3185, GGAATG at 2340, AGAATG at 502.
- TEAr6ci: 1, AGAATG at 993.
- TEAr7ci: 2, AGAATG at 1643, GGAATG at 103.
- TEAr8ci: 4, AGAATG at 2648, GGAATG at 2536, AGAATG at 1295, GGAATG at 157.
- TEAr9ci: 4, AGAATG at 4412, GGAATG at 3677, AGAATG at 2462, GGAATG at 2230.

## TEAr arbitrary (evens) (4560-2846) UTRs
- TEAr0: CATTCC at 3390, CATTCC at 3050.
- TEAr4: CATTCC at 3700.
- TEAr6: CATTCT at 3999, CATTCC at 3690.
- TEAr2ci: GGAATG at 4492, GGAATG at 4356.

## TEAr alternate (odds) (4560-2846) UTRs
- TEAr3: CATTCC at 3472, CATTCC at 3088.
- TEAr5: CATTCC at 3823.
- TEAr9: CATTCC at 3660, CATTCT at 3103.
- TEAr3ci: AGAATG at 4316.
- TEAr5ci: AGAATG at 4340, AGAATG at 3530, GGAATG at 3185.
- TEAr9ci: AGAATG at 4412, GGAATG at 3677.

## TEAr arbitrary positive direction (odds) (4445-4265) core promoters
- TEAr3ci: AGAATG at 4316.
- TEAr5ci: AGAATG at 4340.
- TEAr9ci: AGAATG at 4412.

## TEAr alternate positive direction (evens) (4445-4265) core promoters
- TEAr2ci: GGAATG at 4356.

## TEAr arbitrary negative direction (evens) (2811-2596) proximal promoters
- TEAr4ci: GGAATG at 2701.
- TEAr8ci: AGAATG at 2648.

## TEAr arbitrary negative direction (evens) (2596-1) distal promoters
- TEAr0: CATTCT at 1267, CATTCT at 891.
- TEAr2: CATTCT at 1638, CATTCC at 116.
- TEAr4: CATTCC at 2113, CATTCC at 1552, CATTCT at 310.
- TEAr6: CATTCC at 984.
- TEAr8: CATTCT at 1281.
- TEAr0ci: GGAATG at 1897, AGAATG at 934.
- TEAr4ci: AGAATG at 1100.
- TEAr6ci: AGAATG at 993.
- TEAr8ci: GGAATG at 2536, AGAATG at 1295, GGAATG at 157.

## TEAr alternate negative direction (odds) (2596-1) distal promoters
- TEAr1: CATTCT at 2295, CATTCT at 1318, CATTCC at 774.
- TEAr3: CATTCC at 2348, CATTCC at 1461, CATTCC at 481.
- TEAr7: CATTCT at 2272, CATTCT at 1946, CATTCT at 1018.
- TEAr1ci: AGAATG at 2269.
- TEAr5ci: GGAATG at 2340, AGAATG at 502.
- TEAr7ci: AGAATG at 1643, GGAATG at 103.
- TEAr9ci: AGAATG at 2462, GGAATG at 2230.

## TEAr arbitrary positive direction (odds) (4050-1) distal promoters
- TEAr1: CATTCT at 2295, CATTCT at 1318, CATTCC at 774.
- TEAr3: CATTCC at 3472, CATTCC at 3088, CATTCC at 2348, CATTCC at 1461, CATTCC at 481.
- TEAr5: CATTCC at 3823.
- TEAr7: CATTCT at 2272, CATTCT at 1946, CATTCT at 1018.
- TEAr9: CATTCC at 3660, CATTCT at 3103.
- TEAr1ci: AGAATG at 2269.
- TEAr5ci: AGAATG at 3530, GGAATG at 3185, GGAATG at 2340, AGAATG at 502.
- TEAr7ci: AGAATG at 1643, GGAATG at 103.
- TEAr9ci: GGAATG at 3677, AGAATG at 2462, GGAATG at 2230.

## TEAr alternate positive direction (evens) (4050-1) distal promoters
- TEAr0: CATTCC at 3390, CATTCC at 3050, CATTCT at 1267, CATTCT at 891.
- TEAr2: CATTCT at 1638, CATTCC at 116.
- TEAr4: CATTCC at 3700, CATTCC at 2113, CATTCC at 1552, CATTCT at 310.
- TEAr6: CATTCT at 3999, CATTCC at 3690, CATTCC at 984.
- TEAr8: CATTCT at 1281.
- TEAr0ci: GGAATG at 1897, AGAATG at 934.
- TEAr4ci: GGAATG at 2701, AGAATG at 1100.
- TEAr6ci: AGAATG at 993.
- TEAr8ci: AGAATG at 2648, GGAATG at 2536, AGAATG at 1295, GGAATG at 157.

# TEA analysis and results
"The TEA consensus sequence (TCS) in a fungal TEA/ATTS transcription factor target promoter has been defined as 5CATTCY3 (Andrianopoulos and Timberlake, 1994)."
Comparison:
The occurrences of real TEA positive strand, negative direction UTRs and positive distals are greater than the randoms, negative distals are less than the randoms, negative strand, negative direction UTRS overlap the randoms. This suggests that the real TEAs are likely active or activable.

# Acknowledgements
The content on this page was first contributed by: Henry A. Hoff.