Protein-coding gene in the species Homo sapiens
NFYA |
---|
|
Available structures |
---|
PDB | Ortholog search: PDBe RCSB |
---|
|
|
Identifiers |
---|
Aliases | NFYA, CBF-A, CBF-B, HAP2, NF-YA, nuclear transcription factor Y subunit alpha |
---|
External IDs | OMIM: 189903; MGI: 97316; HomoloGene: 32114; GeneCards: NFYA; OMA:NFYA - orthologs |
---|
Gene location (Human) |
---|
| Chr. | Chromosome 6 (human)[1] |
---|
| Band | 6p21.1 | Start | 41,072,974 bp[1] |
---|
End | 41,102,403 bp[1] |
---|
|
Gene location (Mouse) |
---|
| Chr. | Chromosome 17 (mouse)[2] |
---|
| Band | 17 C|17 23.99 cM | Start | 48,693,913 bp[2] |
---|
End | 48,716,934 bp[2] |
---|
|
RNA expression pattern |
---|
Bgee | Human | Mouse (ortholog) |
---|
Top expressed in | - buccal mucosa cell
- ganglionic eminence
- right testis
- left testis
- sperm
- secondary oocyte
- testicle
- bone marrow cells
- islet of Langerhans
- monocyte
|
| Top expressed in | - secondary oocyte
- primary oocyte
- zygote
- genital tubercle
- tail of embryo
- ganglionic eminence
- thymus
- granulocyte
- yolk sac
- placenta
|
| More reference expression data |
|
---|
BioGPS |
| More reference expression data |
|
---|
|
Gene ontology |
---|
Molecular function | - DNA-binding transcription factor activity
- DNA binding
- core promoter sequence-specific DNA binding
- protein binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
| Cellular component | - CCAAT-binding factor complex
- protein-DNA complex
- nucleus
- nucleoplasm
- RNA polymerase II transcription regulator complex
| Biological process | - positive regulation of transcription, DNA-templated
- regulation of transcription, DNA-templated
- transcription by RNA polymerase II
- transcription, DNA-templated
- rhythmic process
- regulation of cholesterol biosynthetic process
- regulation of transcription by RNA polymerase II
| Sources:Amigo / QuickGO |
|
Orthologs |
---|
Species | Human | Mouse |
---|
Entrez | | |
---|
Ensembl | | |
---|
UniProt | | |
---|
RefSeq (mRNA) | | |
---|
NM_001110832 NM_010913 NM_001347401 NM_001347402 NM_001374803 |
|
---|
RefSeq (protein) | | |
---|
NP_001104302 NP_001334330 NP_001334331 NP_035043 NP_001361732 |
|
---|
Location (UCSC) | Chr 6: 41.07 – 41.1 Mb | Chr 17: 48.69 – 48.72 Mb |
---|
PubMed search | [3] | [4] |
---|
|
Wikidata |
View/Edit Human | View/Edit Mouse |
|
Nuclear transcription factor Y subunit alpha is a protein that in humans is encoded by the NFYA gene.[5][6]
Function
The protein encoded by this gene is one subunit of a trimeric complex NF-Y, forming a highly conserved transcription factor that binds to CCAAT motifs in the promoter regions in a variety of genes.[7] Subunit NFYA associates with a tight dimer composed of the NFYB and NFYC subunits, resulting in a trimer that binds to DNA with high specificity and affinity. The sequence specific interactions of the complex are made by the NFYA subunit, suggesting a role as the regulatory subunit. In addition, there is evidence of post-transcriptional regulation in this gene product, either by protein degradation or control of translation. Further regulation is represented by alternative splicing in the glutamine-rich activation domain, with clear tissue-specific preferences for the two isoforms.[8]
NF-Y complex serves as a pioneer factor by promoting chromatin accessibility to facilitate other co-localizing cell type-specific transcription factors.[9]
NF-Y has also been implicated as a central player in transcription start site (TSS) selection in animals.[10] It safeguards the integrity of the nucleosome-depleted region and PIC localization at protein-coding gene promoters.
Interactions
NFYA has been shown to interact with Serum response factor[11] and ZHX1.[11][12] NFYA, NFYB and NFYC form the NFY complex and it has been shown that the NFY complex serves as a pioneer factor by promoting chromatin accessibility to facilitate other co-localizing cell type-specific transcription factors.[7]
Structure
The atomic structure of the NFY heterotrimer in complex with dsDNA was resolved via X-ray crystallography (PDB ID 4awl).[13] Using one of the NFYA alpha helices as a template, structure inspired stapled peptides were designed to disrupt the NFY heterotrimer formation by preventing NFYA from binding to the NFYB/C heterodimer.[14]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000001167 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023994 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Li XY, Mattei MG, Zaleska-Rutczynska Z, et al. (November 1991). "One subunit of the transcription factor NF-Y maps close to the major histocompatibility complex in murine and human chromosomes". Genomics. 11 (3): 630–634. doi:10.1016/0888-7543(91)90070-U. PMID 1774067.
- ^ Maity SN, de Crombrugghe B (May 1998). "Role of the CCAAT-binding protein CBF/NF-Y in transcription". Trends in Biochemical Sciences. 23 (5): 174–178. doi:10.1016/S0968-0004(98)01201-8. PMID 9612081.
- ^ a b Oldfield AJ, Yang P, Conway AE, et al. (September 2014). "Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors". Molecular Cell. 55 (5): 708–722. doi:10.1016/j.molcel.2014.07.005. PMC 4157648. PMID 25132174.
- ^ "Entrez Gene: NFYA nuclear transcription factor Y, alpha".
- ^ Oldfield AJ, Yang P, Conway AE, et al. (September 2014). "Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors". Molecular Cell. 55 (5): 708–722. doi:10.1016/j.molcel.2014.07.005. PMC 4157648. PMID 25132174. [verification needed]
- ^ Oldfield AJ, Henriques T, Kumar D, et al. (July 2019). "NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region". Nature Communications. 10 (1): 3072. Bibcode:2019NatCo..10.3072O. doi:10.1038/s41467-019-10905-7. PMC 6624317. PMID 31296853.
- ^ a b Yamada K, Osawa H, Granner DK (October 1999). "Identification of proteins that interact with NF-YA". FEBS Letters. 460 (1): 41–45. Bibcode:1999FEBSL.460...41Y. doi:10.1016/S0014-5793(99)01311-3. PMID 10571058. S2CID 28576187.
- ^ Yamada K, Printz RL, Osawa H, et al. (August 1999). "Human ZHX1: cloning, chromosomal location, and interaction with transcription factor NF-Y". Biochemical and Biophysical Research Communications. 261 (3): 614–621. doi:10.1006/bbrc.1999.1087. PMID 10441475.
- ^ Nardini M, Gnesutta N, Donati G, et al. (January 2013). "Sequence-specific transcription factor NF-Y displays histone-like DNA binding and H2B-like ubiquitination". Cell. 152 (1–2): 132–143. doi:10.1016/j.cell.2012.11.047. hdl:2318/1590740. PMID 23332751.
- ^ Jeganathan S, Wendt M, Kiehstaller S, et al. (November 2019). "Constrained Peptides with Fine-Tuned Flexibility Inhibit NF-Y Transcription Factor Assembly". Angewandte Chemie. 58 (48): 17351–17358. doi:10.1002/anie.201907901. PMC 6900064. PMID 31539186.
Further reading
- Mantovani R (October 1999). "The molecular biology of the CCAAT-binding factor NF-Y". Gene. 239 (1): 15–27. doi:10.1016/S0378-1119(99)00368-6. PMID 10571030.
- Li XY, Mantovani R, Hooft van Huijsduijnen R, et al. (March 1992). "Evolutionary variation of the CCAAT-binding transcription factor NF-Y". Nucleic Acids Research. 20 (5): 1087–1091. doi:10.1093/nar/20.5.1087. PMC 312095. PMID 1549471.
- Li XY, Hooft van Huijsduijnen R, Mantovani R, et al. (May 1992). "Intron-exon organization of the NF-Y genes. Tissue-specific splicing modifies an activation domain". The Journal of Biological Chemistry. 267 (13): 8984–8990. doi:10.1016/S0021-9258(19)50377-5. PMID 1577736.
- Becker DM, Fikes JD, Guarente L (March 1991). "A cDNA encoding a human CCAAT-binding protein cloned by functional complementation in yeast". Proceedings of the National Academy of Sciences of the United States of America. 88 (5): 1968–1972. Bibcode:1991PNAS...88.1968B. doi:10.1073/pnas.88.5.1968. PMC 51147. PMID 2000400.
- Vuorio T, Maity SN, de Crombrugghe B (December 1990). "Purification and molecular cloning of the "A" chain of a rat heteromeric CCAAT-binding protein. Sequence identity with the yeast HAP3 transcription factor". The Journal of Biological Chemistry. 265 (36): 22480–22486. doi:10.1016/S0021-9258(18)45730-4. PMID 2266139.
- Mantovani R, Li XY, Pessara U, et al. (August 1994). "Dominant negative analogs of NF-YA". The Journal of Biological Chemistry. 269 (32): 20340–20346. doi:10.1016/S0021-9258(17)31997-X. PMID 8051128.
- Currie RA (December 1997). "Functional interaction between the DNA binding subunit trimerization domain of NF-Y and the high mobility group protein HMG-I(Y)". The Journal of Biological Chemistry. 272 (49): 30880–30888. doi:10.1074/jbc.272.49.30880. PMID 9388234.
- Currie RA (July 1998). "Biochemical characterization of the NF-Y transcription factor complex during B lymphocyte development". The Journal of Biological Chemistry. 273 (29): 18220–18229. doi:10.1074/jbc.273.29.18220. PMID 9660784.
- Roder K, Wolf SS, Larkin KJ, et al. (June 1999). "Interaction between the two ubiquitously expressed transcription factors NF-Y and Sp1". Gene. 234 (1): 61–69. doi:10.1016/S0378-1119(99)00180-8. PMID 10393239.
- Yamada K, Printz RL, Osawa H, et al. (August 1999). "Human ZHX1: cloning, chromosomal location, and interaction with transcription factor NF-Y". Biochemical and Biophysical Research Communications. 261 (3): 614–621. doi:10.1006/bbrc.1999.1087. PMID 10441475.
- Yamada K, Osawa H, Granner DK (October 1999). "Identification of proteins that interact with NF-YA". FEBS Letters. 460 (1): 41–45. Bibcode:1999FEBSL.460...41Y. doi:10.1016/S0014-5793(99)01311-3. PMID 10571058. S2CID 28576187.
- Fan W, Jin S, Tong T, et al. (March 2002). "BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs". The Journal of Biological Chemistry. 277 (10): 8061–8067. doi:10.1074/jbc.M110225200. PMID 11777930.
- Faniello MC, Chirico G, Quaresima B, et al. (April 2002). "An alternative model of H ferritin promoter transactivation by c-Jun". The Biochemical Journal. 363 (Pt 1): 53–58. doi:10.1042/0264-6021:3630053. PMC 1222450. PMID 11903046.
- Bevilacqua MA, Faniello MC, Iovine B, et al. (November 2002). "Transcription factor NF-Y regulates differentiation of CaCo-2 cells". Archives of Biochemistry and Biophysics. 407 (1): 39–44. doi:10.1016/S0003-9861(02)00436-8. PMID 12392713.
- Ge Y, Jensen TL, Matherly LH, et al. (December 2002). "Synergistic regulation of human cystathionine-beta-synthase-1b promoter by transcription factors NF-YA isoforms and Sp1". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1579 (2–3): 73–80. doi:10.1016/s0167-4781(02)00509-2. PMID 12427542.
- Salsi V, Caretti G, Wasner M, et al. (February 2003). "Interactions between p300 and multiple NF-Y trimers govern cyclin B2 promoter function". The Journal of Biological Chemistry. 278 (9): 6642–6650. doi:10.1074/jbc.M210065200. hdl:11380/1202119. PMID 12482752.
- Peng Y, Jahroudi N (March 2003). "The NFY transcription factor inhibits von Willebrand factor promoter activation in non-endothelial cells through recruitment of histone deacetylases". The Journal of Biological Chemistry. 278 (10): 8385–8394. doi:10.1074/jbc.M213156200. PMID 12511565.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
(1) Basic domains |
---|
(1.1) Basic leucine zipper (bZIP) | |
---|
(1.2) Basic helix-loop-helix (bHLH) | Group A | |
---|
Group B | |
---|
Group C bHLH-PAS | |
---|
Group D | |
---|
Group E | |
---|
Group F bHLH-COE | |
---|
|
---|
(1.3) bHLH-ZIP | |
---|
(1.4) NF-1 | |
---|
(1.5) RF-X | |
---|
(1.6) Basic helix-span-helix (bHSH) | |
---|
|
|
(2) Zinc finger DNA-binding domains |
---|
(2.1) Nuclear receptor (Cys4) | subfamily 1 | |
---|
subfamily 2 | |
---|
subfamily 3 | |
---|
subfamily 4 | |
---|
subfamily 5 | |
---|
subfamily 6 | |
---|
subfamily 0 | |
---|
|
---|
(2.2) Other Cys4 | |
---|
(2.3) Cys2His2 | |
---|
(2.4) Cys6 | |
---|
(2.5) Alternating composition | |
---|
(2.6) WRKY | |
---|
|
|
|
(4) β-Scaffold factors with minor groove contacts |
---|
|
|
(0) Other transcription factors |
---|
|
|
see also transcription factor/coregulator deficiencies |
| This article on a gene on human chromosome 6 is a stub. You can help Wikipedia by expanding it. |