White Collar-2 (wc-2) is a gene in Neurospora crassa that codes for the protein WC-2 (54 kDa).[1][2] WC-2 is a GATA transcription factor necessary for regulating circadian rhythms in Frequency (FRQ) expression in fungi.[1] FRQ is a light-induced clock protein involved in an autoregulatory transcription-translation negative feedback loop that controls rhythmic behaviors including conidiation.[3][4] WC-2 binds to its non-redundant counterpart White Collar-1 (WC-1) through PAS domains to form the White Collar Complex (WCC), which is transcriptionally active. In the early subjective night, the WCC binds to the frequency (frq) promoter via zinc finger (ZnF) DNA-binding domains and positively regulates FRQ expression.[1][4] While FRQ and WC-1 are rhythmically expressed, WC-2 is constitutively expressed.[5]
Protein Structure
editWC-2 is a soluble nuclear protein composed of 530 amino acids (aa).[1]
WC-2 has a putative GATA-family ZnF DNA-binding motif that allows the WCC to bind to promoter elements of light-induced genes such as frq. WC-2 also possesses a putative PAS domain that allows protein-protein interactions. WC-2 and WC-1 heterodimerize using PAS domains to form the WCC in vivo.[1]
Function in circadian regulation
editRole of WC-2
editWC-2 has been shown to be necessary for both clock-driven and light-driven expression of frq.[6] While the ZnF and DBD regions of WC-1 are not required for induction of light-responsive genes, the ZnF region of WC-2—which is very similar to that of WC-1 (58% identity match)—is necessary for mediating the association of the frq promoter of WCC in light conditions. WC-2 mutants with altered ZnF and 499-504 aa sequences failed to bind to the frq promoter via the Clock box (C box) and FRQ expression and DNA binding activity were both significantly decreased/impaired; therefore, the WC-2 ZnF and 499-504 aa sequences are essential for FRQ expression in light conditions and for WCC circadian function.[7] A WC-2 null allele (ER33), after hit with a light pulse, showed partial frq transcription induction. This shows that light-driven frq induction is dependent on WC-2; however, it is partially independent of the WC-2 ZnF region, suggesting an alternative mechanism for light-driven frq induction as compared to that of other Neurospora light-induced genes and that of frq regulation in dark conditions.[6]
Interaction between WC-1 and WC-2
editWC-1 is a photopigment that requires flavin adenine dinucleotide (FAD) and blue light to begin its conformational change. After exposure to light, WC-1’s Cys71 residue changes its hydrogen bonding partner. This causes a change in the alpha helix which leads to an open pocket to which WC-2 can bind.[8] In light conditions, WCC takes on the L-WCC conformation, a heterotrimer consisting of two WC-1s and one WC-2. In dark conditions, the WCC adopts a heterodimer conformation, (D-WCC) consisting of WC-1 and WC-2.[7] WC-1 and WC-2 are thought to be the only non-redundant and non-essential genes that are involved in the positive regulation of light-induced carotenogenesis in Neurospora, and are analogous to Clock and Bmal proteins in the Mouse and Drosophila circadian systems in their positive functions in the circadian loops.[6]
See also
editReferences
edit- ^ a b c d e Linden, H.; Macino, G. (1997-01-01). "White collar 2, a partner in blue‐light signal transduction, controlling expression of light–regulated genes in Neurospora crassa". The EMBO Journal. 16 (1): 98–109. doi:10.1093/emboj/16.1.98. ISSN 0261-4189. PMC 1169617. PMID 9009271.
- ^ Ballario, Paola; Talora, Claudio; Galli, Daniela; Linden, Hartmut; Macino, Giuseppe (1998-08-01). "Roles in dimerization and blue light photoresponse of the PAS and LOV domains of Neurospora crassa white collar proteins". Molecular Microbiology. 29 (3): 719–729. doi:10.1046/j.1365-2958.1998.00955.x. ISSN 1365-2958.
- ^ Denault, Deanna L.; Loros, Jennifer J.; Dunlap, Jay C. (2001-01-15). "WC‐2 mediates WC‐1–FRQ interaction within the PAS protein‐linked circadian feedback loop of Neurospora". The EMBO Journal. 20 (1–2): 109–117. doi:10.1093/emboj/20.1.109. ISSN 0261-4189. PMC 140181. PMID 11226161.
- ^ a b Baker, Christopher L.; Loros, Jennifer J.; Dunlap, Jay C. (2012-01-01). "The circadian clock of Neurospora crassa". FEMS Microbiology Reviews. 36 (1): 95–110. doi:10.1111/j.1574-6976.2011.00288.x. ISSN 0168-6445. PMC 3203324. PMID 21707668.
- ^ Denault, Deanna L.; Loros, Jennifer J.; Dunlap, Jay C. (2001-01-15). "WC‐2 mediates WC‐1–FRQ interaction within the PAS protein‐linked circadian feedback loop of Neurospora". The EMBO Journal. 20 (1–2): 109–117. doi:10.1093/emboj/20.1.109. ISSN 0261-4189. PMC 140181. PMID 11226161.
- ^ a b c Collett, Michael A.; Garceau, Norm; Dunlap, Jay C.; Loros, Jennifer J. (2002-01-01). "Light and clock expression of the Neurospora clock gene frequency is differentially driven by but dependent on WHITE COLLAR-2". Genetics. 160 (1): 149–158. ISSN 0016-6731. PMC 1461937. PMID 11805052.
{{cite journal}}: CS1 maint: PMC format (link) - ^ a b Wang, Bin; Zhou, Xiaoying; Loros, Jennifer J.; Dunlap, Jay C. (2016-02-16). "Alternative Use of DNA Binding Domains by the Neurospora White Collar Complex Dictates Circadian Regulation and Light Responses". Molecular and Cellular Biology. 36 (5): 781–793. doi:10.1128/MCB.00841-15. ISSN 0270-7306. PMC 4760224. PMID 26711258.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Larrondo, Luis F.; Olivares-Yañez, Consuelo; Baker, Christopher L.; Loros, Jennifer J.; Dunlap, Jay C. (2015-01-30). "Decoupling circadian clock protein turnover from circadian period determination". Science. 347 (6221): 1257277. doi:10.1126/science.1257277. ISSN 0036-8075. PMC 4432837. PMID 25635104.
{{cite journal}}: CS1 maint: PMC format (link)