Gene transcription factors
A transcription factor is a protein that binds to specific DNA sequences to control the flow (or transcription) of genetic information from DNA to messenger RNA (mRNA).
Transcription factors perform this function alone or with other proteins in a complex, by promoting (as an activator), or blocking (as a repressor) the recruitment of RNA polymerase (the enzyme that performs the transcription of genetic information from DNA to RNA) to specific genes.

# Genetics
Genetics involves the expression, transmission, and variation of inherited characteristics.
Def. a "branch of biology that deals with the transmission and variation of inherited characteristics, in particular chromosomes and DNA" is called genetics.

# Gene transcriptions
Once the DNA double helix and its associated epigenome have been melted so that the template strand is available for binding, a transcription factor binds to a specific nucleotide sequence to biochemically influence gene transcription.

# Theoretical transcription factors
Def. a substance that contains one or more DNA-binding domains that are nucleotide-sequence specific is called a transcription factor.
Def. a protein that binds to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to mRNA is called a transcription factor.

# DNA-binding domains
There are approximately 2600 proteins in the human genome that contain DNA-binding domains, and most of these are presumed to function as transcription factors, though other studies indicate it to be a smaller number. Therefore, approximately 10% of genes in the genome code for transcription factors, which makes this family the single largest family of human proteins. Furthermore, genes are often flanked by several binding sites for distinct transcription factors, and efficient expression of each of these genes requires the cooperative action of several different transcription factors (see, for example, hepatocyte nuclear factors). Hence, the combinatorial use of a subset of the approximately 2000 human transcription factors easily accounts for the unique regulation of each gene in the human genome during development.
A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a general affinity to DNA.

# Regulatory functions
Transcription factors have been classified according to their regulatory function:
- I. constitutively active  present in all cells at all times  general transcription factors, Sp1 transcription factor (Sp1), Nuclear factor 1 (NF1), Ccaat-enhancer-binding proteins (CCAAT)
- II. conditionally active  requires activation
II.A developmental (cell specific)  expression is tightly controlled, but, once expressed, require no additional activation  GATA transcription factor (GATA), hepatocyte nuclear factors (HNF), PIT-1, MyoD, Myf5, Hox, winged-helix transcription factors
II.B signal-dependent  requires external signal for activation
II.B.1 extracellular ligand (endocrine or paracrine)-dependent  nuclear receptors
II.B.2 intracellular ligand (autocrine)-dependent - activated by small intracellular molecules  Sterol regulatory element binding protein (SREBP), p53, orphan nuclear receptors
II.B.3 cell membrane receptor-dependent  second messenger signaling cascades resulting in the phosphorylation of the transcription factor
II.B.3.a resident nuclear factors  reside in the nucleus regardless of activation state  CREB, AP-1, Mef2
II.B.3.b latent cytoplasmic factors  inactive form reside in the cytoplasm, but, when activated, are translocated into the nucleus  STAT, R-SMAD, NF-B, Notch, TUBBY, NFAT
- II.A developmental (cell specific)  expression is tightly controlled, but, once expressed, require no additional activation  GATA transcription factor (GATA), hepatocyte nuclear factors (HNF), PIT-1, MyoD, Myf5, Hox, winged-helix transcription factors
- II.B signal-dependent  requires external signal for activation
II.B.1 extracellular ligand (endocrine or paracrine)-dependent  nuclear receptors
II.B.2 intracellular ligand (autocrine)-dependent - activated by small intracellular molecules  Sterol regulatory element binding protein (SREBP), p53, orphan nuclear receptors
II.B.3 cell membrane receptor-dependent  second messenger signaling cascades resulting in the phosphorylation of the transcription factor
II.B.3.a resident nuclear factors  reside in the nucleus regardless of activation state  CREB, AP-1, Mef2
II.B.3.b latent cytoplasmic factors  inactive form reside in the cytoplasm, but, when activated, are translocated into the nucleus  STAT, R-SMAD, NF-B, Notch, TUBBY, NFAT
- II.B.1 extracellular ligand (endocrine or paracrine)-dependent  nuclear receptors
- II.B.2 intracellular ligand (autocrine)-dependent - activated by small intracellular molecules  Sterol regulatory element binding protein (SREBP), p53, orphan nuclear receptors
- II.B.3 cell membrane receptor-dependent  second messenger signaling cascades resulting in the phosphorylation of the transcription factor
II.B.3.a resident nuclear factors  reside in the nucleus regardless of activation state  CREB, AP-1, Mef2
II.B.3.b latent cytoplasmic factors  inactive form reside in the cytoplasm, but, when activated, are translocated into the nucleus  STAT, R-SMAD, NF-B, Notch, TUBBY, NFAT
- II.B.3.a resident nuclear factors  reside in the nucleus regardless of activation state  CREB, AP-1, Mef2
- II.B.3.b latent cytoplasmic factors  inactive form reside in the cytoplasm, but, when activated, are translocated into the nucleus  STAT, R-SMAD, NF-B, Notch, TUBBY, NFAT

# Sequence similarity
Transcription factors are often classified based on the sequence similarity and hence the tertiary structure of their DNA-binding domains:
- 1 Superclass: Basic Domains
1.1 Class: Leucine zipper factors (bZIP)
1.1.1 Family: AP-1(-like) components; includes (c-Fos/c-Jun)
1.1.2 Family: CREB
1.1.3 Family: Ccaat-enhancer-binding proteins (C/EBP)-like factors
1.1.4 Family: bZIP / PAR
1.1.5 Family: Plant G-box binding factors
1.1.6 Family: ZIP only
1.2 Class: Helix-loop-helix factors (bHLH)
1.2.1 Family: Ubiquitous (class A) factors
1.2.2 Family: Myogenic transcription factors (MyoD)
1.2.3 Family: Achaete-Scute
1.2.4 Family: Tal/Twist/Atonal/Hen
1.3 Class: Helix-loop-helix / leucine zipper factors (basic helix-loop-helix leucine zipper transcription factors (bHLH-ZIP))
1.3.1 Family: Ubiquitous bHLH-ZIP factors; includes USF  (USF1, USF2); SREBP (Sterol regulatory element binding protein (SREBP))
1.3.2 Family: Cell-cycle controlling factors; includes Myc (c-Myc)
1.4 Class: NF-1
1.4.1 Family: NF-1  (NFIA, NFIB, NFIC, NFIX)
1.5 Class: RF-X
1.5.1 Family: RF-X (RFX1, RFX2, RFX3, RFX4, RFX5, RFXANK)
1.6 Class: bHSH
- 1.1 Class: Leucine zipper factors (bZIP)
1.1.1 Family: AP-1(-like) components; includes (c-Fos/c-Jun)
1.1.2 Family: CREB
1.1.3 Family: Ccaat-enhancer-binding proteins (C/EBP)-like factors
1.1.4 Family: bZIP / PAR
1.1.5 Family: Plant G-box binding factors
1.1.6 Family: ZIP only
- 1.1.1 Family: AP-1(-like) components; includes (c-Fos/c-Jun)
- 1.1.2 Family: CREB
- 1.1.3 Family: Ccaat-enhancer-binding proteins (C/EBP)-like factors
- 1.1.4 Family: bZIP / PAR
- 1.1.5 Family: Plant G-box binding factors
- 1.1.6 Family: ZIP only
- 1.2 Class: Helix-loop-helix factors (bHLH)
1.2.1 Family: Ubiquitous (class A) factors
1.2.2 Family: Myogenic transcription factors (MyoD)
1.2.3 Family: Achaete-Scute
1.2.4 Family: Tal/Twist/Atonal/Hen
- 1.2.1 Family: Ubiquitous (class A) factors
- 1.2.2 Family: Myogenic transcription factors (MyoD)
- 1.2.3 Family: Achaete-Scute
- 1.2.4 Family: Tal/Twist/Atonal/Hen
- 1.3 Class: Helix-loop-helix / leucine zipper factors (basic helix-loop-helix leucine zipper transcription factors (bHLH-ZIP))
1.3.1 Family: Ubiquitous bHLH-ZIP factors; includes USF  (USF1, USF2); SREBP (Sterol regulatory element binding protein (SREBP))
1.3.2 Family: Cell-cycle controlling factors; includes Myc (c-Myc)
- 1.3.1 Family: Ubiquitous bHLH-ZIP factors; includes USF  (USF1, USF2); SREBP (Sterol regulatory element binding protein (SREBP))
- 1.3.2 Family: Cell-cycle controlling factors; includes Myc (c-Myc)
- 1.4 Class: NF-1
1.4.1 Family: NF-1  (NFIA, NFIB, NFIC, NFIX)
- 1.4.1 Family: NF-1  (NFIA, NFIB, NFIC, NFIX)
- 1.5 Class: RF-X
1.5.1 Family: RF-X (RFX1, RFX2, RFX3, RFX4, RFX5, RFXANK)
- 1.5.1 Family: RF-X (RFX1, RFX2, RFX3, RFX4, RFX5, RFXANK)
- 1.6 Class: bHSH
- 2 Superclass: Zinc-coordinating DNA-binding domains
2.1 Class: Cys4 zinc finger of nuclear receptor type
2.1.1 Family: Steroid hormone receptors
2.1.2 Family: Thyroid hormone receptor-like factors
2.2 Class: diverse Cys4 zinc fingers
2.2.1 Family: GATA-Factors
2.3 Class: Cys2His2 zinc finger domain
2.3.1 Family: Ubiquitous factors, includes TFIIIA, Sp1
2.3.2 Family: Developmental / cell cycle regulators; includes Kruppel
2.3.4 Family: Large factors with NF-6B-like binding properties
2.4 Class: Cys6 cysteine-zinc cluster
2.5 Class: Zinc fingers of alternating composition
- 2.1 Class: Cys4 zinc finger of nuclear receptor type
2.1.1 Family: Steroid hormone receptors
2.1.2 Family: Thyroid hormone receptor-like factors
- 2.1.1 Family: Steroid hormone receptors
- 2.1.2 Family: Thyroid hormone receptor-like factors
- 2.2 Class: diverse Cys4 zinc fingers
2.2.1 Family: GATA-Factors
- 2.2.1 Family: GATA-Factors
- 2.3 Class: Cys2His2 zinc finger domain
2.3.1 Family: Ubiquitous factors, includes TFIIIA, Sp1
2.3.2 Family: Developmental / cell cycle regulators; includes Kruppel
2.3.4 Family: Large factors with NF-6B-like binding properties
- 2.3.1 Family: Ubiquitous factors, includes TFIIIA, Sp1
- 2.3.2 Family: Developmental / cell cycle regulators; includes Kruppel
- 2.3.4 Family: Large factors with NF-6B-like binding properties
- 2.4 Class: Cys6 cysteine-zinc cluster
- 2.5 Class: Zinc fingers of alternating composition
- 3 Superclass: Helix-turn-helix
3.1 Class: Homeobox (Homeo domain)
3.1.1 Family: Homeo domain only; includes Ubx
3.1.2 Family: POU family (POU domain) factors; includes Octamer transcription factor (Oct)
3.1.3 Family: Homeo domain with LIM region
3.1.4 Family: homeo domain plus zinc finger motifs
3.2 Class: Paired box
3.2.1 Family: Paired plus homeo domain
3.2.2 Family: Paired domain only
3.3 Class: FOX proteins (Fork head) / winged helix
3.3.1 Family: Developmental regulators; includes forkhead
3.3.2 Family: Tissue-specific regulators
3.3.3 Family: Cell-cycle controlling factors
3.3.0 Family: Other regulators
3.4 Class: Heat Shock Factors
3.4.1 Family: HSF
3.5 Class: Tryptophan clusters
3.5.1 Family: Myb
3.5.2 Family: Ets-type
3.5.3 Family: Interferon regulatory factors
3.6 Class: TEA (transcriptional enhancer factor) domain
3.6.1 Family: TEA (TEAD1, TEAD2, TEAD3, TEAD4)
- 3.1 Class: Homeobox (Homeo domain)
3.1.1 Family: Homeo domain only; includes Ubx
3.1.2 Family: POU family (POU domain) factors; includes Octamer transcription factor (Oct)
3.1.3 Family: Homeo domain with LIM region
3.1.4 Family: homeo domain plus zinc finger motifs
- 3.1.1 Family: Homeo domain only; includes Ubx
- 3.1.2 Family: POU family (POU domain) factors; includes Octamer transcription factor (Oct)
- 3.1.3 Family: Homeo domain with LIM region
- 3.1.4 Family: homeo domain plus zinc finger motifs
- 3.2 Class: Paired box
3.2.1 Family: Paired plus homeo domain
3.2.2 Family: Paired domain only
- 3.2.1 Family: Paired plus homeo domain
- 3.2.2 Family: Paired domain only
- 3.3 Class: FOX proteins (Fork head) / winged helix
3.3.1 Family: Developmental regulators; includes forkhead
3.3.2 Family: Tissue-specific regulators
3.3.3 Family: Cell-cycle controlling factors
3.3.0 Family: Other regulators
- 3.3.1 Family: Developmental regulators; includes forkhead
- 3.3.2 Family: Tissue-specific regulators
- 3.3.3 Family: Cell-cycle controlling factors
- 3.3.0 Family: Other regulators
- 3.4 Class: Heat Shock Factors
3.4.1 Family: HSF
- 3.4.1 Family: HSF
- 3.5 Class: Tryptophan clusters
3.5.1 Family: Myb
3.5.2 Family: Ets-type
3.5.3 Family: Interferon regulatory factors
- 3.5.1 Family: Myb
- 3.5.2 Family: Ets-type
- 3.5.3 Family: Interferon regulatory factors
- 3.6 Class: TEA (transcriptional enhancer factor) domain
3.6.1 Family: TEA (TEAD1, TEAD2, TEAD3, TEAD4)
- 3.6.1 Family: TEA (TEAD1, TEAD2, TEAD3, TEAD4)
- 4 Superclass: beta-Scaffold Factors with Minor Groove Contacts
4.1 Class: RHR (Rel homology region)
4.1.1 Family: Rel/ankyrin; NF-B
4.1.2 Family: ankyrin only
4.1.3 Family: NFAT (Nuclear Factor of Activated T-cells) (NFATC1, NFATC2, NFATC3, NFATC4, NFAT5)
4.2 Class: STAT
4.2.1 Family: STAT
4.3 Class: p53
4.3.1 Family: p53
4.4 Class: MADS box
4.4.1 Family: Regulators of differentiation; includes (Mef2)
4.4.2 Family: Responders to external signals, SRF (serum response factor)
4.4.3 Family: Metabolic regulators (ARG80)
4.5 Class: beta-Barrel alpha-helix transcription factors
4.6 Class: TATA binding proteins
4.6.1 Family: TBP
4.7 Class: HMG-box
4.7.1 Family: SOX genes, SRY
4.7.2 Family: TCF-1 (HNF1A specifically TCF1)
4.7.3 Family: HMG2-related, Structure specific recognition protein 1 (SSRP1)
4.7.4 Family: UBF
4.7.5 Family: MATA
4.8 Class: Heteromeric CCAAT factors
4.8.1 Family: Heteromeric CCAAT factors
4.9 Class: Grainyhead
4.9.1 Family: Grainyhead
4.10 Class: Cold-shock domain factors
4.10.1 Family: csd
4.11 Class: Runt
4.11.1 Family: Runt
- 4.1 Class: RHR (Rel homology region)
4.1.1 Family: Rel/ankyrin; NF-B
4.1.2 Family: ankyrin only
4.1.3 Family: NFAT (Nuclear Factor of Activated T-cells) (NFATC1, NFATC2, NFATC3, NFATC4, NFAT5)
- 4.1.1 Family: Rel/ankyrin; NF-B
- 4.1.2 Family: ankyrin only
- 4.1.3 Family: NFAT (Nuclear Factor of Activated T-cells) (NFATC1, NFATC2, NFATC3, NFATC4, NFAT5)
- 4.2 Class: STAT
4.2.1 Family: STAT
- 4.2.1 Family: STAT
- 4.3 Class: p53
4.3.1 Family: p53
- 4.3.1 Family: p53
- 4.4 Class: MADS box
4.4.1 Family: Regulators of differentiation; includes (Mef2)
4.4.2 Family: Responders to external signals, SRF (serum response factor)
4.4.3 Family: Metabolic regulators (ARG80)
- 4.4.1 Family: Regulators of differentiation; includes (Mef2)
- 4.4.2 Family: Responders to external signals, SRF (serum response factor)
- 4.4.3 Family: Metabolic regulators (ARG80)
- 4.5 Class: beta-Barrel alpha-helix transcription factors
- 4.6 Class: TATA binding proteins
4.6.1 Family: TBP
- 4.6.1 Family: TBP
- 4.7 Class: HMG-box
4.7.1 Family: SOX genes, SRY
4.7.2 Family: TCF-1 (HNF1A specifically TCF1)
4.7.3 Family: HMG2-related, Structure specific recognition protein 1 (SSRP1)
4.7.4 Family: UBF
4.7.5 Family: MATA
- 4.7.1 Family: SOX genes, SRY
- 4.7.2 Family: TCF-1 (HNF1A specifically TCF1)
- 4.7.3 Family: HMG2-related, Structure specific recognition protein 1 (SSRP1)
- 4.7.4 Family: UBF
- 4.7.5 Family: MATA
- 4.8 Class: Heteromeric CCAAT factors
4.8.1 Family: Heteromeric CCAAT factors
- 4.8.1 Family: Heteromeric CCAAT factors
- 4.9 Class: Grainyhead
4.9.1 Family: Grainyhead
- 4.9.1 Family: Grainyhead
- 4.10 Class: Cold-shock domain factors
4.10.1 Family: csd
- 4.10.1 Family: csd
- 4.11 Class: Runt
4.11.1 Family: Runt
- 4.11.1 Family: Runt
- 0 Superclass: Other Transcription Factors
0.1 Class: Copper fist proteins
0.2 Class: HMGI(Y) (HMGA1)
0.2.1 Family: HMGI(Y)
0.3 Class: Pocket domain
0.4 Class: E1A-like factors
0.5 Class: AP2/EREBP-related factors
0.5.1 Family: Apetala 2 (AP2)
0.5.2 Family: EREBP
0.5.3 Superfamily: B3 DNA-binding domain (AP2/B3)
0.5.3.1 Family: ARF
0.5.3.2 Family: ABI
0.5.3.3 Family: RAV
- 0.1 Class: Copper fist proteins
- 0.2 Class: HMGI(Y) (HMGA1)
0.2.1 Family: HMGI(Y)
- 0.2.1 Family: HMGI(Y)
- 0.3 Class: Pocket domain
- 0.4 Class: E1A-like factors
- 0.5 Class: AP2/EREBP-related factors
0.5.1 Family: Apetala 2 (AP2)
0.5.2 Family: EREBP
0.5.3 Superfamily: B3 DNA-binding domain (AP2/B3)
0.5.3.1 Family: ARF
0.5.3.2 Family: ABI
0.5.3.3 Family: RAV
- 0.5.1 Family: Apetala 2 (AP2)
- 0.5.2 Family: EREBP
- 0.5.3 Superfamily: B3 DNA-binding domain (AP2/B3)
0.5.3.1 Family: ARF
0.5.3.2 Family: ABI
0.5.3.3 Family: RAV
- 0.5.3.1 Family: ARF
- 0.5.3.2 Family: ABI
- 0.5.3.3 Family: RAV

# General transcription factors
"General transcription factors (GTFs), also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites on DNA to activate transcription. GTFs, RNA polymerase, and the mediator multiple protein complex constitute the basic transcriptional apparatus."

# Hypotheses
- Some transcription factors transcribe A1BG.