Nuclear transcription factor Y subunit alpha is a protein that in humans is encoded by the NFYAgene.[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]
^"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. PMID1774067.
^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. PMID9612081.
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. PMID10393239.
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. PMID10441475.
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. PMID12392713.
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. PMID12427542.
