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.
Interactionsedit
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]
Structureedit
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]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000001167 - Ensembl, May 2017
^ abcGRCm38: 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): 630–4. 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): 174–8. doi:10.1016/S0968-0004(98)01201-8. PMID 9612081.
^ abOldfield 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. PMC4157648. 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): 708–22. doi:10.1016/j.molcel.2014.07.005. PMC4157648. PMID 25132174. [verification needed]
^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. PMC6624317. PMID 31296853.
^ abYamada 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.
^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.
^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.
^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. PMC6900064. PMID 31539186.
Further readingedit
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. PMC312095. 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. PMC51147. 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. PMC1222450. 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.
nfya, nuclear, transcription, factor, subunit, alpha, protein, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes4awlidentifiersaliases, hap2, nuclear, transcription, factor, subunit, alphaexternal, idsomim, 189903, 97. Nuclear transcription factor Y subunit alpha is a protein that in humans is encoded by the NFYA gene 5 6 NFYAAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes4AWLIdentifiersAliasesNFYA CBF A CBF B HAP2 NF YA nuclear transcription factor Y subunit alphaExternal IDsOMIM 189903 MGI 97316 HomoloGene 32114 GeneCards NFYAGene location Human Chr Chromosome 6 human 1 Band6p21 1Start41 072 974 bp 1 End41 102 403 bp 1 Gene location Mouse Chr Chromosome 17 mouse 2 Band17 C 17 23 99 cMStart48 693 913 bp 2 End48 716 934 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inganglionic eminencespermsecondary oocytebone marrow cellsislet of Langerhansmonocytestromal cell of endometriummiddle temporal gyrusrectumbloodTop expressed insecondary oocyteganglionic eminencethymusyolk sacplacentabone marrowovaryuterusspleenlensMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionDNA 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 specificCellular componentCCAAT binding factor complex protein DNA complex nucleus nucleoplasm RNA polymerase II transcription regulator complexBiological processpositive 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 IISources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez480018044EnsemblENSG00000001167ENSMUSG00000023994UniProtP23511P23708RefSeq mRNA NM 021705NM 002505NM 001110832NM 010913NM 001347401NM 001347402NM 001374803RefSeq protein NP 002496NP 068351NP 001104302NP 001334330NP 001334331NP 035043NP 001361732Location UCSC Chr 6 41 07 41 1 MbChr 17 48 69 48 72 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Interactions 3 Structure 4 References 5 Further reading 6 External linksFunction editThe 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 editNFYA 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 editThe 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 edit 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 4 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 8 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 22 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 22 doi 10 1016 j molcel 2014 07 005 PMC 4157648 PMID 25132174 verification needed 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 a b 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 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 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 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 editMantovani 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 editNFYA protein human at the U S National Library of Medicine Medical Subject Headings MeSH FactorBook NF YAThis article incorporates text from the United States National Library of Medicine which is in the public domain nbsp This article on a gene on human chromosome 6 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title NFYA amp oldid 1218378275, wikipedia, wiki, book, books, library,
