Disease relevance of NFYB

• Chromosomal translocations involving the human CBFB gene, which codes for the non-DNA binding subunit of CBF (CBF beta), are associated with a large percentage of human leukemias [1].
• In contrast, the CBFbeta-smooth muscle myosin heavy chain (SMMHC) fusion protein generated by the inv(16) associated with acute myeloid leukemias (M4Eo) cannot rescue definitive hematopoiesis by Cbfb-deficient ES cells [2].

High impact information on NFYB

• This higher affinity provides an explanation for the dominant negative phenotype associated with a knock-in of the CBFB-MYH11 gene and also helps to provide a rationale for the leukemia-associated dysregulation of hematopoietic development that this protein causes [1].
• We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series [3].
• Role of Cbfb in hematopoiesis and perturbations resulting from expression of the leukemogenic fusion gene Cbfb-MYH11 [4].
• This population of stem cells and progenitors was not present in mouse embryos heterozygous for the Cbfb-MYH11 knock-in gene [4].
• Definitive hematopoiesis is restored by ectopic expression of full-length Cbfb transgenes, as well as by a transgene encoding only the heterodimerization domain of CBFbeta [2].

Biological context of NFYB

• Hence, this study demonstrates that the heterotrimeric CBF protein consists of two transcription activation domains, one present in CBF-B and the other in CBF-C, and that the two domains act additively in the in vitro assay [5].
• We first used a heterologous system in which a series of deletion mutations of CBF-B, fused to the bacterial LexA DNA binding domain, were transfected into HeLa cells together with a reporter gene driven by a minimal promoter containing LexA binding sites [6].
• The role of CBF in activating transcription was further substantiated by inhibition of promoter activity with a plasmid expressing a dominant negative CBF-B mutant [7].
• This study suggested that the activation domain of CBF-B plays an essential role in the transcription activation of Cyclin B1 and Aurora A genes at G2/M phase, thus regulating cell cycle progression at G2/M phase [8].
• Homozygous disruption of either the Runx1 or Cbfb gene in mice results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system, and severely impairs fetal liver hematopoiesis [2].

Anatomical context of NFYB

• Temperature may influence and regulate NF-YB expression in toad oocyte [9].
• In this study, we used a tetracycline-inducible adenoviral vector to express a truncated CBF-B subunit, Bdbd, lacking a transcription activation domain in various mammalian cell lines [8].
• To confirm native HAP3 functionality, we quantitated mRNA expression in uncultured PBMCs and in laser microdissected normal lung epithelial cells (MNLEC) from the same patients [10].

Associations of NFYB with chemical compounds

• These experiments showed that CBF-B needed both a glutamine-rich domain and an adjacent serine/threonine-rich domain to activate the reporter gene optimally [6].
• We then tested whether in this system the glutamine- and serine/threonine-rich domains of CBF-B were needed for trans-activation by CBF [6].
• We also show that in vitro-translated NF-YB specifically bound to a glutathione S-transferase-Tax1 fusion protein [11].
• After culture and in vitro exposure to sulforaphane, BITC, or EGCG, the elevated GSTP1 mRNA expression of PBMCs from HAP3 individuals decreased to common expression levels [10].
• These results clearly demonstrate that NF-YB and thymosin beta-10 are specific cellular binding proteins of HMN-154 and that this shared region is necessary for the binding to HMN-154 [12].

Physical interactions of NFYB

• However, NF-YB did interact with the C-terminal Tax1 mutants M22 (130TL-AS) and M47 (319LL-RS) [11].
• In yeast two-hybrid assays HSP-CBF interacts with NF-YB [13].
• We have isolated three genes that potentially encode a HAP3/nuclear factor-YB (NF-YB)/CCAAT binding factor-A (CBF-A) subunit of a CCAAT-box binding complex in rice (Oryza sativa), and named them OsHAP3A, OsHAP3B and OsHAP3C [14].
• EMSA supershift analyses indicate that a protein immunologically related to NF-YB is part of the specific nuclear protein complex binding the human CYP1A1 NRE [15].

Other interactions of NFYB

• Recombinant full-length CBF-B together with CBF-A and CBF-C activated transcription of several alpha 2(I) collagen gene promoter constructs [6].
• Further, Tax1 coimmunoprecipitated with NF-Y from nuclear extracts of HTLV-1-transformed cells, providing evidence for in vivo interaction of Tax1 and NF-YB [11].
• This suggested that dbpB may complete with NF-YB for interaction with NF-YA [16].
• The NF-YB and NF-YC subunits have histone fold motifs with a high degree of homology to NC2alpha/beta, a TBP-binding repressor [17].
• We conclude that specificity of the NF-Y trimer is not due to NF-YA only, but stems in part from the contribution of the histone fold alpha1, particularly that of NF-YB [17].

Analytical, diagnostic and therapeutic context of NFYB

• In addition, by electrophoretic mobility shift assay, ICE3 was recognized by a protein complex containing NF-YB that was present at reduced levels in the topoIIalpha-overexpressing CEM/ICRF-8 extracts, suggesting that ICE3 plays a negative regulatory role in human topoIIalpha gene expression [18].
• Reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis showed a CBFB-MYH11 fusion transcript and MYH11 rearrangement, respectively, in all three cases [19].
• Among these, a flax gene of the non-LEC1-like HAP3 family and a flax MYB factor were shown to be expressed in specialized tissues of flax embryo using an in situ hybridization approach [20].

References