The transactivation domain or trans-activating domain (TAD) is a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

scaffold domain which contains binding sites for other

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s such as

transcription coregulator In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription ar ...

s. These binding sites are frequently referred to as activation functions (AFs). TADs are named after their amino acid composition. These amino acids are either essential for the activity or simply the most abundant in the TAD. Transactivation by the Gal4 transcription factor is mediated by acidic

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s, whereas hydrophobic residues in

Gcn4 Gcn4 is a transcription factor and a “master regulator” for gene expression which regulates close to one tenth of the yeast genome. In a study by Razaghi et al, amino acid starvation activated the transcription factor Gcn4p, resulting in tran ...

play a similar role. Hence, the TADs in Gal4 and Gcn4 are referred to as acidic or hydrophobic, respectively. In general we can distinguish four classes of TADs: * acidic domains (called also “acid blobs” or “negative noodles", rich in D and E amino acids, present in Gal4, Gcn4 and VP16). * glutamine-rich domains (contains multiple repetitions like "QQQXXXQQQ", present in SP1) * proline-rich domains (contains repetitions like "PPPXXXPPP" present in

c-jun Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only l ...

, AP2 and

Oct-2 Oct-2 (octamer-binding protein 2) also known as POU domain, class 2, transcription factor 2 is a protein that in humans is encoded by the POU2F2 gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredit ...

) * isoleucine-rich domains (repetitions "IIXXII", present in NTF-1) Alternatively, since similar amino acid compositions does not necessarily mean similar activation pathways, TADs can be grouped by the process they stimulate, either

initiation Initiation is a rite of passage marking entrance or acceptance into a group or society. It could also be a formal admission to adulthood in a community or one of its formal components. In an extended sense, it can also signify a transformatio ...

or elongation.

Acidic/9aaTAD

Nine-amino-acid transactivation domain (9aaTAD) defines a domain common to a large superfamily of eukaryotic transcription factors represented by Gal4, Oaf1, Leu3, Rtg3, Pho4, Gln3,

in yeast, and by

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

NFAT Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the developme ...

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription (genetics), transcription of DNA, cytokine production and cell survival. NF-κB is found i ...

and VP16 in mammals. The definition largely overlaps with an "acidic" family definition. A 9aaTAD prediction tool is available. 9aaTADs tend to have an associated 3-aa hydrophobic (usually Leu-rich) region immediately to its N-terminal. 9aaTAD transcription factors

, VP16, MLL, E2A,

HSF1 Heat shock factor protein 1 (HSF 1) is a protein that in humans is encoded by the ''HSF1'' gene. HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-st ...

, NF-IL6, NFAT1 and

interact directly with the general coactivators

TAF9 TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 32kDa, also known as TAF9, is a protein that in humans is encoded by the ''TAF9'' gene. Function Initiation of transcription by RNA polymerase II requires the activities ...

and

CBP/p300 The p300-CBP coactivator family in humans is composed of two closely related transcriptional co-activating proteins (or coactivators): #p300 (also called EP300 or E1A binding protein p300) # CBP (also known as CREB-binding protein or CREBBP) ...

. p53 9aaTADs interact with TAF9, GCN5 and with multiple domains of CBP/p300 (KIX, TAZ1,TAZ2 and IBiD). The KIX domain of general coactivators Med15(Gal11) interacts with 9aaTAD transcription factors Gal4, Pdr1, Oaf1,

, VP16, Pho4, Msn2, Ino2 and P201. Positions 1, 3-4, and 7 of the 9aaTAD are the main residues that interact with KIX. Interactions of Gal4, Pdr1 and Gcn4 with Taf9 have been observed. 9aaTAD is a common transactivation domain which recruits multiple general coactivators

, MED15,

and

GCN5 __NOTOC__ Histone acetyltransferase KAT2A is an enzyme that in humans is encoded by the ''KAT2A'' gene. Interactions GCN5L2 has been shown to interact with: * DDB1, * Ku70, * Ku80, * TADA2L, * TAF9, and * Transcription initiation protein ...

Glutamine-rich

Glutamine (Q)-rich TADs are found in

POU2F1 POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the ''POU2F1'' gene. Interactions POU2F1 has been shown to interact with: * EPRS, * Glucocorticoid receptor, * Glyceraldehyde 3-phosphate dehydrogenase, ...

(Oct1), POU2F2 (Oct2), and Sp1 (see also Sp/KLF family). Although such is not the case for every Q-rich TAD, Sp1 is shown to interact with

TAF4 Transcription initiation factor TFIID subunit 4 is a protein that in humans is encoded by the ''TAF4'' gene. Function Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coord ...

(TAFII 130), a part of the

TFIID Transcription factor II D (TFIID) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. RNA polymerase II holoenzyme is a form of eukaryotic RNA polymerase II that is recruited to the promoters ...

assembly.

References

{{reflist, 35em

External links

9aaTAD prediction tool
Transcription factors Protein domains

Acidic/9aaTAD

Glutamine-rich

See also

References

External links