NFYA

NFYA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4AWL
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
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 ganglionic eminence sperm secondary oocyte bone marrow cells islet of Langerhans monocyte stromal cell of endometrium middle temporal gyrus rectum blood Top expressed in secondary oocyte ganglionic eminence thymus yolk sac placenta bone marrow ovary uterus spleen lens 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 4800 18044 Ensembl ENSG00000001167 ENSMUSG00000023994 UniProt P23511 P23708 RefSeq (mRNA) NM_021705 NM_002505 NM_001110832 NM_010913 NM_001347401 NM_001347402 NM_001374803 RefSeq (protein) NP_002496 NP_068351 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

1. GRCh38: Ensembl release 89: ENSG00000001167 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000023994 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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): 630–4. doi:10.1016/0888-7543(91)90070-U. PMID   1774067.
6. Maity SN, de Crombrugghe B (May 1998). "Role of the CCAAT-binding protein CBF/NF-Y in transcription". Trends in Biochemical Sciences. 23 (5): 174–8. doi:10.1016/S0968-0004(98)01201-8. PMID   9612081.
7. 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): 708–22. doi:10.1016/j.molcel.2014.07.005. PMC   4157648 . PMID   25132174.
8. "Entrez Gene: NFYA nuclear transcription factor Y, alpha".
9. 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): 708–22. doi:10.1016/j.molcel.2014.07.005. PMC   4157648 . PMID   25132174.^{[ verification needed ]}
10. Oldfield AJ, Henriques T, Burkholder AB, et al. (11 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.
11. Yamada K, Osawa H, Granner DK (October 1999). "Identification of proteins that interact with NF-YA". FEBS Letters. 460 (1): 41–5. doi: 10.1016/S0014-5793(99)01311-3 . PMID   10571058. S2CID   28576187.
12. 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): 614–21. doi:10.1006/bbrc.1999.1087. PMID   10441475.
13. Nardini M, Gnesutta N, Donati G, et al. (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 . ISSN   0092-8674. PMID   23332751.
14. 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): 1087–91. 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): 8984–90. 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): 1968–72. 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): 22480–6. 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): 20340–6. 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): 30880–8. 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): 18220–9. 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): 61–9. 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): 614–21. 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): 41–5. 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): 8061–7. 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): 53–8. 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): 6642–50. 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): 8385–94. doi: 10.1074/jbc.M213156200 . PMID   12511565.

External links

• NFYA+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook NF-YA

This article incorporates text from the United States National Library of Medicine, which is in the public domain.