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Published online before print October 31, 2007, 10.1101/gad.1608807
GENES & DEVELOPMENT 21:2936-2949, 2007
©2007 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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Transcription of histone gene cluster by differential core-promoter factors

Yoh Isogai1, Sündüz Keles2, Matthias Prestel3, Andreas Hochheimer3, and Robert Tjian1,4,5,6

1 Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA; 2 Department of Statistics, Department of Biostatistics, and Department of Medical Informatics, University of Wisconsin at Madison, Madison, Wisconsin 53706, USA; 3 Adolf-Butenandt-Institut, Molekularbiologie, 80336 Munich, Germany; 4 Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, California 94720, USA; 5 Li Ka-Shing Center for Biomedical and Health Sciences, University of California at Berkeley, Berkeley, California 94720, USA

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.

[Keywords: TATA-box-binding protein (TBP); TBP-related factor 2 (TRF2); core-promoter recognition; histone gene cluster; ChIP-on-chip; chromatin organization]]

Received August 24, 2007; revised version accepted September 21, 2007.


6 Corresponding author.

E-MAIL jmlim{at}berkeley.edu; FAX (510) 643-9547.

Supplemental material is available at http://www.genesdev.org.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1608807


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