NFYA

{{Short description|Protein-coding gene in the species Homo sapiens}}

Nuclear transcription factor Y subunit alpha is a protein that in humans is encoded by the NFYA gene.{{cite journal | vauthors = Li XY, Mattei MG, Zaleska-Rutczynska Z, Hooft van Huijsduijnen R, Figueroa F, Nadeau J, Benoist C, Mathis D | title = One subunit of the transcription factor NF-Y maps close to the major histocompatibility complex in murine and human chromosomes | journal = Genomics | volume = 11 | issue = 3 | pages = 630–634 | date = November 1991 | pmid = 1774067 | doi = 10.1016/0888-7543(91)90070-U }}{{cite journal | vauthors = Maity SN, de Crombrugghe B | title = Role of the CCAAT-binding protein CBF/NF-Y in transcription | journal = Trends in Biochemical Sciences | volume = 23 | issue = 5 | pages = 174–178 | date = May 1998 | pmid = 9612081 | doi = 10.1016/S0968-0004(98)01201-8 }}

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.{{cite journal | vauthors = Oldfield AJ, Yang P, Conway AE, Cinghu S, Freudenberg JM, Yellaboina S, Jothi R | title = Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors | journal = Molecular Cell | volume = 55 | issue = 5 | pages = 708–722 | date = September 2014 | pmid = 25132174 | pmc = 4157648 | doi = 10.1016/j.molcel.2014.07.005 }} 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.{{cite web | title = Entrez Gene: NFYA nuclear transcription factor Y, alpha| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4800}}

NF-Y complex serves as a pioneer factor by promoting chromatin accessibility to facilitate other co-localizing cell type-specific transcription factors.{{cite journal | vauthors = Oldfield AJ, Yang P, Conway AE, Cinghu S, Freudenberg JM, Yellaboina S, Jothi R | title = Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors | journal = Molecular Cell | volume = 55 | issue = 5 | pages = 708–722 | date = September 2014 | pmid = 25132174 | pmc = 4157648 | doi = 10.1016/j.molcel.2014.07.005 }} {{verify source |date=September 2019 |reason=This ref was deleted Special:Diff/905782955 by a bug in VisualEditor and later restored by a bot from the original cite located at Special:Permalink/885362148 cite #7 – verify the cite is accurate and delete this template. User:GreenC bot/Job 18}}

NF-Y has also been implicated as a central player in transcription start site (TSS) selection in animals.{{cite journal | vauthors = Oldfield AJ, Henriques T, Kumar D, Burkholder AB, Cinghu S, Paulet D, Bennett BD, Yang P, Scruggs BS, Lavender CA, Rivals E, Adelman K, Jothi R | title = NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region | journal = Nature Communications | volume = 10 | issue = 1 | pages = 3072 | date = July 2019 | pmid = 31296853 | pmc = 6624317 | doi = 10.1038/s41467-019-10905-7 | doi-access = free | bibcode = 2019NatCo..10.3072O }} 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{{cite journal | vauthors = Yamada K, Osawa H, Granner DK | title = Identification of proteins that interact with NF-YA | journal = FEBS Letters | volume = 460 | issue = 1 | pages = 41–45 | date = October 1999 | pmid = 10571058 | doi = 10.1016/S0014-5793(99)01311-3 | s2cid = 28576187 | doi-access = free | bibcode = 1999FEBSL.460...41Y }} and ZHX1.{{cite journal | vauthors = Yamada K, Printz RL, Osawa H, Granner DK | title = Human ZHX1: cloning, chromosomal location, and interaction with transcription factor NF-Y | journal = Biochemical and Biophysical Research Communications | volume = 261 | issue = 3 | pages = 614–621 | date = August 1999 | pmid = 10441475 | doi = 10.1006/bbrc.1999.1087 }} 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.

Structure

The atomic structure of the NFY heterotrimer in complex with dsDNA was resolved via X-ray crystallography ([https://www.rcsb.org/structure/4AWL PDB ID 4awl]).{{cite journal | vauthors = Nardini M, Gnesutta N, Donati G, Gatta R, Forni C, Fossati A, Vonrhein C, Moras D, Romier C, Bolognesi M, Mantovani R | title = Sequence-specific transcription factor NF-Y displays histone-like DNA binding and H2B-like ubiquitination | journal = Cell | volume = 152 | issue = 1–2 | pages = 132–143 | date = January 2013 | pmid = 23332751 | doi = 10.1016/j.cell.2012.11.047 | hdl-access = free | hdl = 2318/1590740 }} 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.{{cite journal | vauthors = Jeganathan S, Wendt M, Kiehstaller S, Brancaccio D, Kuepper A, Pospiech N, Carotenuto A, Novellino E, Hennig S, Grossmann TN | title = Constrained Peptides with Fine-Tuned Flexibility Inhibit NF-Y Transcription Factor Assembly | journal = Angewandte Chemie | volume = 58 | issue = 48 | pages = 17351–17358 | date = November 2019 | pmid = 31539186 | pmc = 6900064 | doi = 10.1002/anie.201907901 }}

References

External links

{{MeshName|NFYA+protein,+human}}
{{FactorBook|NF-YA}}

Category:Transcription factors