Transcription of histone gene cluster by differential core-promoter factors.
The 100 copies of tandemly arrayed Drosophila linker (H1) and core (H2A/B and H3/H4) histone gene cluster are coordinately regulated during the cell cycle. However, the molecular mechanisms that must allow differential transcription of linker versus core histones prevalent during development remain elusive. Here, we used fluorescence imaging, biochemistry, and genetics to show that TBP (TATA-box-binding protein)-related factor 2 (TRF2) selectively regulates the TATA-less Histone H1 gene promoter, while TBP/TFIID targets core histone transcription. Importantly, TRF2-depleted polytene chromosomes display severe chromosomal structural defects. This selective usage of TRF2 and TBP provides a novel mechanism to differentially direct transcription within the histone cluster. Moreover, genome-wide chromatin immunoprecipitation (ChIP)-on-chip analyses coupled with RNA interference (RNAi)-mediated functional studies revealed that TRF2 targets several classes of TATA-less promoters of >1000 genes including those driving transcription of essential chromatin organization and protein synthesis genes. Our studies establish that TRF2 promoter recognition complexes play a significantly more central role in governing metazoan transcription than previously appreciated.
Isogai
Yoh
Y
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.
Keles
Sündüz
S
Prestel
Matthias
M
Hochheimer
Andreas
A
Tjian
Robert
R
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D002875:Chromosomes; D016000:Cluster Analysis; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D017344:Genes, Insect; D017930:Genes, Reporter; D006657:Histones / Q000235:genetics*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D049409:Luciferases, Firefly / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012689:Sequence Homology, Nucleic Acid; D035182:TATA Box Binding Protein-Like Proteins / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000378:metabolism; D014158:Transcription, Genetic
D006657:Histones; D035182:TATA Box Binding Protein-Like Proteins; D035181:TATA-Box Binding Protein; D049409:Luciferases, Firefly