# Gene transcriptions/USFs

"A major environmental stress encountered by humans is solar UV light, which can cause skin inflammation, the induction of pro-inflammatory cytokines and skin ageing, as well as skin cancer, including the highly aggressive and increasingly common malignant melanoma (Elwood, 1996; Armstrong et al., 1997; Park and Gilchrest, 1999). The serious adverse effect of UV light on the skin has meant that humans have evolved an effective defence mechanism. In response to low levels of UV irradiation epidermal melanocytes increase the production of the pigment melanin in specialized organelles termed melanosomes (Jimbow et al., 1991). The melanosomes are transferred into surrounding keratinocytes where they act to protect against UV-induced DNA damage."
"The Tyrosinase gene encodes the rate-limiting enzyme for the production of melanin and is absolutely required for pigmentation; the absence of a functional tyrosinase enzyme results in an albino phenotype. Although much of the tanning response comprises a post-translational activation of the melanosome, transcription of the Tyrosinase gene is UV responsive (Hara et al., 1994; Sturm et al., 1994; Imokawa et al., 1995, 1997; Ota et al., 1998). However, analysis of the Tyrosinase promoter (Bentley et al., 1994; Ganss et al., 1994) failed to reveal any classical UV or stress-response element. The human Tyrosinase promoter comprises an SP1 site and two E box motifs, one at the initiator, and a second, termed the M box (Lowings et al., 1992), located at –100 with respect to the transcription initiation site (Bentley et al., 1994). The E box motifs are essential for Tyrosinase promoter activity and are highly evolutionarily conserved. Numerous studies (Bentley et al., 1994; Ganss et al., 1994; Hemesath et al., 1994; Yasumoto et al., 1994; Yavuzer et al., 1995; Krylov et al., 1997) have demonstrated that the Tyrosinase initiator E box and M box elements are targets for the microphthalmia-associated basic helix–loop–helix-leucine zipper (bHLH-LZ) transcription factor Mitf (Hodgkinson et al., 1993; Hughes et al., 1993). In addition to its role in regulating pigmentation genes, [the microphthalmia-associated transcription factor] Mitf is also critically required for the development of the melanocyte (Steingrímsson et al., 1994; Opdecamp et al., 1997)."
The "UV response is mediated by the ubiquitous bHLH-LZ transcription factor [upstream stimulatory factor] Usf-1, which, like Mitf, binds the conserved E box elements in the Tyrosinase promoter. The ability of Usf-1 to activate transcription is regulated by a signal transduction pathway that culminates in phosphorylation and activation of Usf-1 by the p38 stress-activated kinase."
"Usf-1 and Usf-2 bind the Tyrosinase promoter in vivo."
"USF comprises a combination of related ubiquitous bHLH-LZ transcription factors encoded by the Usf-1 and Usf-2 genes (Gregor et al., 1990; Sirito et al., 1992, 1994). Usf-1 and Usf-2 can form either homo- or heterodimers (Sirito et al., 1992; Viollet et al., 1996), and both are present in melanocytes and melanoma cell lines [...]."

## Human genes

Gene ID: 7391 is USF1 upstream transcription factor 1 (aka upstream stimulatory factor 1). "This gene encodes a member of the basic helix-loop-helix leucine zipper family, and can function as a cellular transcription factor. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs. This gene has been linked to familial combined hyperlipidemia (FCHL). Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been defined on chromosome 21."
* NP_009053.1 upstream stimulatory factor 1 isoform 1 (variant 1).
* NP_996888.1 upstream stimulatory factor 1 isoform 2 (variant 2).
* NP_001263302.1 upstream stimulatory factor 1 isoform 1 (variant 3).
Gene ID: 7392 is USF2 upstream transcription factor 2, c-fos interacting. "This gene encodes a member of the basic helix-loop-helix leucine zipper family of transcription factors. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs and is involved in regulating multiple cellular processes."
* NP_003358.1 upstream stimulatory factor 2 isoform 1.
* NP_997174.1 upstream stimulatory factor 2 isoform 2.
* NP_001308079.1 upstream stimulatory factor 2 isoform 3.
* XP_024307452.1 upstream stimulatory factor 2 isoform X1.
* XP_005259254.1 upstream stimulatory factor 2 isoform X2.
* XP_024307453.1 upstream stimulatory factor 2 isoform X3.
* XP_016882688.1 upstream stimulatory factor 2 isoform X4.
* XP_011525562.1 upstream stimulatory factor 2 isoform X5.
* XP_011525563.1 upstream stimulatory factor 2 isoform X6.
Gene ID: 205717 is USF3 upstream transcription factor family member 3. "This gene encodes a large protein that contains a helix-loop-helix domain and a polyglutamine region. A deletion in the polyglutamine region was associated with risk for thyroid carcinoma."
* NP_001009899.3 basic helix-loop-helix domain-containing protein USF3 (variant 1).
* NR_111981.1 RNA Sequence (non-coding, variant 2).
* XP_024309159.1 basic helix-loop-helix domain-containing protein USF3 isoform X1.
* XP_024309160.1 basic helix-loop-helix domain-containing protein USF3 isoform X2.
* XP_016861360.1 basic helix-loop-helix domain-containing protein USF3 isoform X1.
* XP_016861361.1 basic helix-loop-helix domain-containing protein USF3 isoform X2.
* XP_005247265.2 basic helix-loop-helix domain-containing protein USF3 isoform X2.
Gene ID: 100151645 is USF1P1 upstream transcription factor 1 pseudogene 1.