Alternative titles; symbols
HGNC Approved Gene Symbol: GTF2A1L
Cytogenetic location: 2p16.3 Genomic coordinates (GRCh38) : 2:48,617,856-48,679,604 (from NCBI)
Synthesis of eukaryotic mRNA requires the assembly of RNA polymerase II and various general transcription factors, such as the TFIIA subunits alpha/beta (GTF2A1; 600520) and gamma (GTF2A2; 600519), which interact with the TATA-binding protein (TBP; 600075) and a separate 4-helix bundle positioned just upstream of the TBP-TATA complex. ALF is a germ cell-specific transcription factor with a domain structure similar to GTF2A1 (Upadhyaya et al., 1999).
By searching databases for genes similar to GTF2A1, followed by 5-prime RACE of a testis cDNA library, Upadhyaya et al. (1999) cloned ALF. The 478-amino acid protein has a calculated molecular mass of 53 kD. In comparison with the organization of GTF2A1, ALF has conserved regions I and IV and acidic region III, but it has a distinct region II. Northern and dot blot analyses showed strong testis-restricted expression of a 1.8-kb ALF transcript, which differed from the widespread expression of GTF2A1 and GTF2A2. SDS-PAGE analysis revealed a 69-kD ALF protein. Upadhyaya et al. (1999) suggested that the difference between the calculated and observed molecular masses may be due to the effect of charged region III.
Han et al. (2001) cloned mouse Alf. The mouse protein shares highest similarity with human ALF in regions I and IV. Northern blot analysis of mouse and rat tissues detected expression only in testis. Expression was first detected in mouse testis at postnatal day 14. Sedimentation analysis and in situ hybridization showed that Alf was expressed in pachytene spermatocytes and haploid spermatids.
In the process of cloning ALF, Upadhyaya et al. (1999) also cloned a longer transcript, SALF, containing most of the ALF sequence at its 3-prime end. Han et al. (2001) determined that SALF is a chimeric transcript that contains exons 1 through 3 of STON1 (605357) spliced to exons 2 through 9 of ALF. See 605357 for further information on SALF.
Using gel shift analysis, Upadhyaya et al. (1999) demonstrated that, like GTF2A1, ALF, in conjunction with GTF2A2 and TBP, bound DNA. Functional analysis showed that ALF, together with GTF2A2, allowed mRNA transcription.
Upadhyaya et al. (2002) found that mammalian ALF was able to stabilize the binding of TBP to DNA, but it could not stabilize several TBP mutants. Phosphorylation of ALF with casein kinase II (see CSNK2A1; 115440) resulted in partial restoration of complex formation using mutant TBPs. Studies of ALF-TBP complexes formed on the adenovirus major late promoter revealed protection of the TATA box and upstream sequences from -38 to -20 on the top strand and -40 to -22 on the bottom strand. The presence of ALF or TFIIA did not significantly alter the ability of TBP to bind TATA elements from several testis specific genes. Analysis of the distinct, nonhomologous internal regions II of ALF and GTF2A1 using circular dichroism spectroscopy suggested that these domains are unordered. Upadhyaya et al. (2002) concluded that the role of ALF in the assembly and stabilization of initiation complexes in germ cells is likely to be similar or identical to the role of TFIIA in somatic cells.
Han et al. (2001) determined that the ALF gene contains 9 exons.
By PCR of a panel of human-rodent chromosomal hybrids and genomic sequence analysis, Han et al. (2001) mapped the GTF2A1L gene to chromosome 2p.
Han, S.-Y., Zhou, L., Upadhyaya, A., Lee, S. H., Parker, K. L., DeJong, J. TFIIA-alpha/beta-like factor is encoded by a germ cell-specific gene whose expression is up-regulated with other general transcription factors during spermatogenesis in the mouse. Biol. Reprod. 64: 507-517, 2001. [PubMed: 11159353] [Full Text: https://doi.org/10.1095/biolreprod64.2.507]
Upadhyaya, A. B., Khan, M., Mou, T.-C., Junker, M., Gray, D. M., DeJong, J. The germ cell-specific transcription factor ALF: structural properties and stabilization of the Tata-binding protein (TBP)-DNA complex. J. Biol. Chem. 277: 34208-34216, 2002. [PubMed: 12107178] [Full Text: https://doi.org/10.1074/jbc.M204808200]
Upadhyaya, A. B., Lee, S. H., DeJong, J. Identification of a general transcription factor TFIIA-alpha/beta homolog selectively expressed in testis. J. Biol. Chem. 274: 18040-18048, 1999. [PubMed: 10364255] [Full Text: https://doi.org/10.1074/jbc.274.25.18040]