TCCAAT-HAP2 ranscription Factor Family
Proteins that bind to the CCAAT motif were first characterized in the yeast
Saccharomyces cerevisiae through analysis of mutants with reduced levels of expression
of the CYC1 gene (encoding iso-1-Cyt c) (Guarente et al., 1984; Hahn et al., 1988). The
CYC1 promoter comprises two UAS, one of which (UAS2) contains an inverted CCAAT motif
that is required for UAS2-directed transcription. Activation of transcription from UAS2
requires HAP2, HAP3, and HAP5 (Pinkham and Guarente, 1985; Pinkham et al., 1987; Hahn
et al., 1988; McNabb et al., 1995), which form a heterotrimeric CCAAT-box-binding
complex. The yeast HAP complex recruits a fourth polypeptide, HAP4 (Forsburg and
Guarente, 1989), which does not bind to DNA but associates with the HAP2,3,5 complex
and activates transcription through an acidic domain. The HAP complex appears to
control expression of genes important for mitochondrial biogenesis (de Winde and
Grivell, 1993), demonstrated by the fact that yeast hap mutants show identical
pleiotropic phenotypes, with a general reduction in cytochromes and reduced growth on
nonfermentable carbon sources.
CCAAT-box-related motifs have also been identified in the promoters of a variety of
vertebrate genes. A range of transcription factors has been shown to bind to different
CCAAT boxes, with varying levels of specificity (Dorn et al., 1987; Raymondjean et al.,
1988), and each is thought to play a distinct role in gene expression or DNA
replication (Santoro et al., 1988). Direct homologs of the yeast HAP complex (called
NF-Y, CP1, or CBF) have been identified in vertebrates (Maity et al., 1990; Becker et
al., 1991; Li et al., 1992; Sinha et al., 1995). The individual vertebrate HAP subunits
showed a remarkable similarity to the yeast homologs over short domains (Maity et al.,
1990; Vuorio et al., 1990), which is sufficient to enable formation of a functional
heterologous complex between the human HAP2 homolog and yeast HAP3 and HAP5 (Becker et
al., 1991). However, outside of the highly conserved core protein motifs associated
with DNA binding and subunit interactions, there is considerable divergence.
Furthermore, there is no HAP4 homolog. Instead, the vertebrate HAP complex probably
interacts with other classes of transcription factors to influence the level of
transcription (Bellorini et al., 1997).
Based on their presence in other eukaryotes and sequence conservation between related
plant gene promoters, putative CCAAT-box motifs have been identified for several plant
genes (Rieping and Sch?ffl, 1992; Kehoe et al., 1994; Ito et al., 1995). As with
vertebrates, there is no unifying expression pattern for plant genes containing
putative CCAAT-promoter elements, indicating that they may play a complex role in
regulating plant gene transcription, with greater similarity to the vertebrate model
than to the yeast system. A homolog with sequence similarity to HAP3 has been isolated
from maize (Li et al., 1992), and recently, a HAP2 homolog was characterized from
Brassica napus (Albani and Robert, 1995).
Over 40 CCAAT-HAP2 TF family identified via searching with domains of:
13 CCAAT-HAP2 protein
and DNA
sequences
with
annotations for soybean in PlantTFDB. Most are partial sequences.
Last updated by Dr. Xianfeng (Jeff) Chen on June 7, 2009.