Gcn4

Fungal protein found in Saccharomyces cerevisiae S288c

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,^[1] amino acid starvation activated the transcription factor Gcn4p, resulting in transcriptional induction of almost all genes involved in amino acid biosynthesis, including HIS4. Thus involvement of Gcn4 in regulation of both histidinol dehydrogenase HIS4 and interferon gamma hIFNγ was hypothesised as a scenario explaining the increased level of hIFNγ under amino acid starvation.^[1]

Gcn4 is a highly conserved protein and its mammalian homolog is known as activating transcription factor-4 (ATF4).^[2]

Overexpression of Gcn4 leads to the reduction in protein synthesis capacity which contributes to Gcn4-mediated increase of yeast lifespan.^[3]

In budding yeast, deletion of Gcn4 prevents HIS4 from targeting to the nuclear periphery upon transcriptional activation, indicating that Gcn4 is necessary for regulation of gene positioning and transcription.^[4]

External links

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)

Activating transcription factor
- AATF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
AP-1
- c-Fos
- FOSB
- FOSL1
- FOSL2
- JDP2
- c-Jun
- JUNB
- JunD
BACH
- 1
- 2
BATF
BLZF1
C/EBP
- α
- β
- γ
- δ
- ε
- ζ
CREB
- 1
- 3
- L1
CREM
DBP
DDIT3
GABPA
GCN4
HLF
MAF
- B
- F
- G
- K
NFE
- 2
- L1
- L2
- L3
NFIL3
NRL
NRF
- 1
- 2
- 3
XBP1

(1.2) Basic helix-loop-helix (bHLH)

Group A	AS-C ASCL1 ASCL2 ATOH1 HAND 1 2 MESP2 Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 NeuroD 1 2 Neurogenins 1 2 3 OLIG 1 2 Paraxis TCF15 Scleraxis SLC LYL1 TAL 1 2 Twist
Group B	FIGLA Myc c-Myc l-Myc n-Myc MXD4 TCF4
Group C bHLH-PAS	AhR AHRR ARNT ARNTL ARNTL2 CLOCK HIF 1A EPAS1 3A NPAS 1 2 3 PER 1 2 3 Period SIM 1 2
Group D	BHLH 2 3 9 Pho4 ID 1 2 3 4
Group E	HES 1 2 3 4 5 6 7 HEY 1 2 L
Group F bHLH-COE	EBF1

(1.3) bHLH-ZIP

AP-4
MAX
- MXD1
- MXD3
MITF
MNT
MLX
MLXIPL
MXI1
Myc
SREBP
- 1
- 2
USF1

(1.4) NF-1

NFI
- A
- B
- C
- X
SMAD
- R-SMAD
  - 1
  - 2
  - 3
  - 5
  - 9
- I-SMAD
  - 6
  - 7
- 4)

(1.5) RF-X

RFX
- 1
- 2
- 3
- 4
- 5
- 6
- ANK

(1.6) Basic helix-span-helix (bHSH)

AP-2
- α
- β
- γ
- δ
- ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR
subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX
subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ
subfamily 4	NUR NGFIB NOR1 NURR1
subfamily 5	LRH-1 SF1
subfamily 6	GCNF
subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
Sp/KLF family
- KLF
  - 1
  - 2
  - 3
  - 4
  - 5
  - 6
  - 7
  - 8
  - 9
  - 10
  - 11
  - 12
  - 13
  - 14
  - 15
  - 17
- SP
  - 1
  - 2
  - 4
  - 7
  - 8
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 21
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655
- 804A

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain

Antennapedia
ANTP class

protoHOX Hox-like	ParaHox Gsx 1 2 Xlox PDX1 Cdx 1 2 4 extended Hox: Evx1 Evx2 MEOX1 MEOX2 Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 GBX1 GBX2 MNX1
metaHOX NK-like	BARHL1 BARHL2 BARX1 BARX2 BSX DBX 1 2 DLX 1 2 3 4 5 6 EMX 1 2 EN 1 2 HHEX HLX LBX1 LBX2 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 HMX1 HMX2 HMX3 6-1 6-2 NATO TLX1 TLX2 TLX3 VAX1 VAX2

other

ARX
CRX
CUTL1
FHL
- 1
- 2
- 3
HESX1
HOPX
LMX
- 1A
- 1B
NOBOX
TALE
- IRX
  - 1
  - 2
  - 3
  - 4
  - 5
  - 6
  - MKX
- MEIS
  - 1
  - 2
- PBX
  - 1
  - 2
  - 3
- PKNOX
  - 1
  - 2
- SIX
  - 1
  - 2
  - 3
  - 4
  - 5
PHF
- 1
- 3
- 6
- 8
- 10
- 16
- 17
- 20
- 21A
POU domain
- PIT-1
- BRN-3: A
- B
- C
- Octamer transcription factor: 1
- 2
- 3/4
- 6
- 7
- 11
SATB2
ZEB
- 1
- 2

(3.2) Paired box

PAX
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
PRRX
- 1
- 2
PROP1
PHOX
- 2A
- 2B
RAX
SHOX
SHOX2
VSX1
VSX2
Bicoid
- GSC
- BICD2
- OTX
  - 1
  - 2
- PITX
  - 1
  - 2
  - 3

(3.3) Fork head / winged helix

E2F
- 1
- 2
- 3
- 4
- 5
FOX proteins
- A1
- A2
- A3
- B1
- B2
- C1
- C2
- D1
- D2
- D3
- D4
- D4L1
- D4L3
- D4L4
- D4L5
- D4L6
- E1
- E3
- F1
- F2
- G1
- H1
- I1
- I2
- I3
- J1
- J2
- J3
- K1
- K2
- L1
- L2
- M1
- N1
- N2
- N3
- N4
- O1
- O3
- O4
- O6
- P1
- P2
- P3
- P4
- Q1
- R1
- R2
- S1

(3.4) Heat shock factors

HSF
- 1
- 2
- 4

(3.5) Tryptophan clusters

ELF
- 2
- 4
- 5
EGF
ELK
- 1
- 3
- 4
ERF
ETS
- 1
- 2
- ERG
- SPIB
ETV
- 1
- 4
- 5
- 6
FLI1
Interferon regulatory factors
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
MYB
MYBL2

(3.6) TEA domain

transcriptional enhancer factor
- 1
- 2
- 3
- 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5
(4.2) STAT	STAT 1 2 3 4 5 6
(4.3) p53-like	p53 p63 p73 family p53 TP63 p73 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF
(4.4) MADS box	Mef2 A B C D SRF
(4.6) TATA-binding proteins	TBP TBPL1
(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF/LEF TCF 1 3 4 LEF1 TOX 1 2 3 4
(4.9) Grainyhead	TFCP2
(4.10) Cold-shock domain	CSDA YBX1
(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1
(0.3) Pocket domain	Rb RBL1 RBL2
(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3
(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

References

^ ^a ^b Razaghi, Ali; Huerlimann, Roger; Owens, Leigh; Heimann, Kirsten (1 December 2015). "Increased expression and secretion of recombinant hIFNγ through amino acid starvation-induced selective pressure on the adjacent HIS4 gene in Pichia pastoris". Acta Facultatis Pharmaceuticae Universitatis Comenianae. 62 (2): 43–50. doi:10.1515/afpuc-2015-0031.
^ Murguía, José R.; Serrano, Ramón (2012). "New functions of protein kinase Gcn2 in yeast and mammals". IUBMB Life. 64 (12): 971–974. doi:10.1002/iub.1090. PMID 23129244.
^ Mittal, Nitish; Guimaraes, Joao C.; Gross, Thomas; Schmidt, Alexander; Vina-Vilaseca, Arnau; Nedialkova, Danny D.; Aeschimann, Florian; Leidel, Sebastian A.; Spang, Anne; Zavolan, Mihaela (2017). "The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan". Nature Communications. 8 (1): 457. Bibcode:2017NatCo...8..457M. doi:10.1038/s41467-017-00539-y. PMC 5587724. PMID 28878244.
^ Randise-Hinchliff, Carlo; Brickner, Jason H. (2016). "Transcription factors dynamically control the spatial organization of the yeast genome". Nucleus. 7 (4): 369–374. doi:10.1080/19491034.2016.1212797. PMC 5039007. PMID 27442220.