The transactivation domain or trans-activating domain (TAD) is a
transcription factorscaffold domain which contains binding sites for other
proteins such as
transcription coregulators. These binding sites are frequently referred to as activation functions (AFs).[1] 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 acids, whereas hydrophobic residues in
Gcn4 play a similar role. Hence, the TADs in Gal4 and
Gcn4 are referred to as acidic or hydrophobic, respectively.[2][3][4][5][6][7][8][9]
In general we can distinguish four classes of TADs:[10]
acidic domains (called also “acid blobs” or “negative noodles", rich in D and E amino acids, present in Gal4, Gcn4 and VP16).[11]
glutamine-rich domains (contains multiple repetitions like "QQQXXXQQQ", present in
SP1)[12]
proline-rich domains (contains repetitions like "PPPXXXPPP" present in
c-jun,
AP2 and
Oct-2)[13]
isoleucine-rich domains (repetitions "IIXXII", present in
NTF-1)[14]
Alternatively, since similar amino acid compositions does not necessarily mean similar activation pathways, TADs can be grouped by the process they stimulate, either initiation or elongation.[15]
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,
Gcn4 in yeast, and by
p53,
NFAT,
NF-κB and
VP16 in mammals. The definition largely overlaps with an "acidic" family definition. A 9aaTAD prediction tool is available.[16] 9aaTADs tend to have an associated 3-aa hydrophobic (usually Leu-rich) region immediately to its N-terminal.[17]
Glutamine (Q)-rich TADs are found in
POU2F1 (Oct1),
POU2F2 (Oct2), and
Sp1 (see also
Sp/KLF family).[12] Although such is not the case for every Q-rich TAD, Sp1 is shown to interact with
TAF4 (TAFII 130), a part of the
TFIID assembly.[15][53]
^
abCourey AJ, Holtzman DA, Jackson SP, Tjian R (December 1989). "Synergistic activation by the glutamine-rich domains of human transcription factor Sp1". Cell. 59 (5): 827–36.
doi:
10.1016/0092-8674(89)90606-5.
PMID2512012.
S2CID2910480.
^Mermod N, O'Neill EA, Kelly TJ, Tjian R (August 1989). "The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain". Cell. 58 (4): 741–53.
doi:
10.1016/0092-8674(89)90108-6.
PMID2504497.
S2CID22817940.
^
abcPiskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (Jun 2007). "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics. 89 (6): 756–68.
doi:
10.1016/j.ygeno.2007.02.003.
PMID17467953.
^Uesugi M, Nyanguile O, Lu H, Levine AJ, Verdine GL (Aug 1997). "Induced alpha helix in the VP16 activation domain upon binding to a human TAF". Science. 277 (5330): 1310–3.
doi:
10.1126/science.277.5330.1310.
PMID9271577.
^Brüschweiler S, Schanda P, Kloiber K, Brutscher B, Kontaxis G, Konrat R, Tollinger M (Mar 2009). "Direct observation of the dynamic process underlying allosteric signal transmission". Journal of the American Chemical Society. 131 (8): 3063–8.
doi:
10.1021/ja809947w.
PMID19203263.
^Liu GH, Qu J, Shen X (May 2008). "NF-kappaB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1783 (5): 713–27.
doi:
10.1016/j.bbamcr.2008.01.002.
PMID18241676.
^Badi L, Barberis A (Aug 2001). "Proteins that genetically interact with the Saccharomyces cerevisiae transcription factor Gal11p emphasize its role in the initiation-elongation transition". Molecular Genetics and Genomics. 265 (6): 1076–86.
doi:
10.1007/s004380100505.
PMID11523780.
S2CID19287634.
^Kim YJ, Björklund S, Li Y, Sayre MH, Kornberg RD (May 1994). "A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II". Cell. 77 (4): 599–608.
doi:
10.1016/0092-8674(94)90221-6.
PMID8187178.
S2CID5002125.
^Lim MK, Tang V, Le Saux A, Schüller J, Bongards C, Lehming N (Nov 2007). "Gal11p dosage-compensates transcriptional activator deletions via Taf14p". Journal of Molecular Biology. 374 (1): 9–23.
doi:
10.1016/j.jmb.2007.09.013.
PMID17919657.
^Lallet S, Garreau H, Garmendia-Torres C, Szestakowska D, Boy-Marcotte E, Quevillon-Chéruel S, Jacquet M (Oct 2006). "Role of Gal11, a component of the RNA polymerase II mediator in stress-induced hyperphosphorylation of Msn2 in Saccharomyces cerevisiae". Molecular Microbiology. 62 (2): 438–52.
doi:
10.1111/j.1365-2958.2006.05363.x.
PMID17020582.
^Mizuno T, Harashima S (Apr 2003). "Gal11 is a general activator of basal transcription, whose activity is regulated by the general repressor Sin4 in yeast". Molecular Genetics and Genomics. 269 (1): 68–77.
doi:
10.1007/s00438-003-0810-x.
PMID12715155.
S2CID882139.
^Thakur JK, Arthanari H, Yang F, Pan SJ, Fan X, Breger J, Frueh DP, Gulshan K, Li DK, Mylonakis E, Struhl K, Moye-Rowley WS, Cormack BP, Wagner G, Näär AM (Apr 2008). "A nuclear receptor-like pathway regulating multidrug resistance in fungi". Nature. 452 (7187): 604–9.
Bibcode:
2008Natur.452..604T.
doi:
10.1038/nature06836.
PMID18385733.
S2CID205212715.
The transactivation domain or trans-activating domain (TAD) is a
transcription factorscaffold domain which contains binding sites for other
proteins such as
transcription coregulators. These binding sites are frequently referred to as activation functions (AFs).[1] 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 acids, whereas hydrophobic residues in
Gcn4 play a similar role. Hence, the TADs in Gal4 and
Gcn4 are referred to as acidic or hydrophobic, respectively.[2][3][4][5][6][7][8][9]
In general we can distinguish four classes of TADs:[10]
acidic domains (called also “acid blobs” or “negative noodles", rich in D and E amino acids, present in Gal4, Gcn4 and VP16).[11]
glutamine-rich domains (contains multiple repetitions like "QQQXXXQQQ", present in
SP1)[12]
proline-rich domains (contains repetitions like "PPPXXXPPP" present in
c-jun,
AP2 and
Oct-2)[13]
isoleucine-rich domains (repetitions "IIXXII", present in
NTF-1)[14]
Alternatively, since similar amino acid compositions does not necessarily mean similar activation pathways, TADs can be grouped by the process they stimulate, either initiation or elongation.[15]
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,
Gcn4 in yeast, and by
p53,
NFAT,
NF-κB and
VP16 in mammals. The definition largely overlaps with an "acidic" family definition. A 9aaTAD prediction tool is available.[16] 9aaTADs tend to have an associated 3-aa hydrophobic (usually Leu-rich) region immediately to its N-terminal.[17]
Glutamine (Q)-rich TADs are found in
POU2F1 (Oct1),
POU2F2 (Oct2), and
Sp1 (see also
Sp/KLF family).[12] Although such is not the case for every Q-rich TAD, Sp1 is shown to interact with
TAF4 (TAFII 130), a part of the
TFIID assembly.[15][53]
^
abCourey AJ, Holtzman DA, Jackson SP, Tjian R (December 1989). "Synergistic activation by the glutamine-rich domains of human transcription factor Sp1". Cell. 59 (5): 827–36.
doi:
10.1016/0092-8674(89)90606-5.
PMID2512012.
S2CID2910480.
^Mermod N, O'Neill EA, Kelly TJ, Tjian R (August 1989). "The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain". Cell. 58 (4): 741–53.
doi:
10.1016/0092-8674(89)90108-6.
PMID2504497.
S2CID22817940.
^
abcPiskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (Jun 2007). "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics. 89 (6): 756–68.
doi:
10.1016/j.ygeno.2007.02.003.
PMID17467953.
^Uesugi M, Nyanguile O, Lu H, Levine AJ, Verdine GL (Aug 1997). "Induced alpha helix in the VP16 activation domain upon binding to a human TAF". Science. 277 (5330): 1310–3.
doi:
10.1126/science.277.5330.1310.
PMID9271577.
^Brüschweiler S, Schanda P, Kloiber K, Brutscher B, Kontaxis G, Konrat R, Tollinger M (Mar 2009). "Direct observation of the dynamic process underlying allosteric signal transmission". Journal of the American Chemical Society. 131 (8): 3063–8.
doi:
10.1021/ja809947w.
PMID19203263.
^Liu GH, Qu J, Shen X (May 2008). "NF-kappaB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1783 (5): 713–27.
doi:
10.1016/j.bbamcr.2008.01.002.
PMID18241676.
^Badi L, Barberis A (Aug 2001). "Proteins that genetically interact with the Saccharomyces cerevisiae transcription factor Gal11p emphasize its role in the initiation-elongation transition". Molecular Genetics and Genomics. 265 (6): 1076–86.
doi:
10.1007/s004380100505.
PMID11523780.
S2CID19287634.
^Kim YJ, Björklund S, Li Y, Sayre MH, Kornberg RD (May 1994). "A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II". Cell. 77 (4): 599–608.
doi:
10.1016/0092-8674(94)90221-6.
PMID8187178.
S2CID5002125.
^Lim MK, Tang V, Le Saux A, Schüller J, Bongards C, Lehming N (Nov 2007). "Gal11p dosage-compensates transcriptional activator deletions via Taf14p". Journal of Molecular Biology. 374 (1): 9–23.
doi:
10.1016/j.jmb.2007.09.013.
PMID17919657.
^Lallet S, Garreau H, Garmendia-Torres C, Szestakowska D, Boy-Marcotte E, Quevillon-Chéruel S, Jacquet M (Oct 2006). "Role of Gal11, a component of the RNA polymerase II mediator in stress-induced hyperphosphorylation of Msn2 in Saccharomyces cerevisiae". Molecular Microbiology. 62 (2): 438–52.
doi:
10.1111/j.1365-2958.2006.05363.x.
PMID17020582.
^Mizuno T, Harashima S (Apr 2003). "Gal11 is a general activator of basal transcription, whose activity is regulated by the general repressor Sin4 in yeast". Molecular Genetics and Genomics. 269 (1): 68–77.
doi:
10.1007/s00438-003-0810-x.
PMID12715155.
S2CID882139.
^Thakur JK, Arthanari H, Yang F, Pan SJ, Fan X, Breger J, Frueh DP, Gulshan K, Li DK, Mylonakis E, Struhl K, Moye-Rowley WS, Cormack BP, Wagner G, Näär AM (Apr 2008). "A nuclear receptor-like pathway regulating multidrug resistance in fungi". Nature. 452 (7187): 604–9.
Bibcode:
2008Natur.452..604T.
doi:
10.1038/nature06836.
PMID18385733.
S2CID205212715.