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NFYA

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NFYA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNFYA, CBF-A, CBF-B, HAP2, NF-YA, nuclear transcription factor Y subunit alpha
External IDsOMIM: 189903; MGI: 97316; HomoloGene: 32114; GeneCards: NFYA; OMA:NFYA - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 MbChr 17: 48.69 – 48.72 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Nuclear transcription factor Y subunit alpha is a protein that in humans is encoded by the NFYA gene.[5][6]

Function

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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

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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

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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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000001167Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023994Ensembl, 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): 630–634. 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): 174–178. doi:10.1016/S0968-0004(98)01201-8. PMID 9612081.
  7. ^ 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.
  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): 708–722. doi:10.1016/j.molcel.2014.07.005. PMC 4157648. PMID 25132174. [verification needed]
  10. ^ 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.
  11. ^ 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.
  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): 614–621. doi:10.1006/bbrc.1999.1087. PMID 10441475.
  13. ^ 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.
  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

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