In their upcoming G&D paper, Dr. Robert Tjian (UC Berkeley) and colleagues reveal how histone gene expression is differentially regulated during Drosophila development. The researchers demonstrate that different basal transcription factors drive expression of the histone gene cluster, lending new insight into the regulation of metazoan transcription.
"This study surprised us on 2 levels; one was the preponderance of TRF2 dependent promoters; the other was the differential usage of TRF2 versus TBP within a gene cluster generally thought to be coordinately regulated. Just goes to show that dogma shifts constantly in this field of transcriptional control, explains Dr. Tjian.
In eukaryotic cells, gene transcription is initiated when the RNA polymerase II machinery recognizes and binds to specific core promoter sequences in the gene. While some genes contain a TATA box core promoter element that is recognized by TBP (the TATA-box binding polypeptide), the majority of core promoters fall into various TATA-less categories. A family of TBP-related factors (called TRFs) have been identified, but their core promoter recognition functions have not yet been elucidated.
In this paper, Dr. Tjian and colleagues identify novel TRF2 target promoters, effectively distinguishing between three classes of genes: TBP-dependent ones, TRF2-dependent ones and a small class genes that utilize both TBP and TRF2. They show that TRF2 is used as an alternative core promoter recognition factor to drive transcription of the TATA-less Histone H1 gene, while the other core Histone genes (H2A, H2B, H3 and H4) are dependent upon TBP. Furthermore, depletion of TRF2 in Drosophila cells resulted in reduced ribosomal gene transcription, abnormal cell changes and chromosomal defects.
|Contact: Heather Cosel|
Cold Spring Harbor Laboratory