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Human U2 snRNA Genes Exhibit a Persistently Open Transcriptional State and Promoter Disassembly at Metaphase

Thomas Pavelitz, Arnold D. Bailey, Christopher P. Elco, and Alan M. Weiner^*

Department of Biochemistry, School of Medicine, University of Washington, Seattle, Washington 98195-7350

Received 16 January 2008/ Returned for modification 26 February 2008/ Accepted 23 March 2008

In mammals, small multigene families generate spliceosomal U snRNAs that are nearly as abundant as rRNA. Using the tandemly repeated human U2 genes as a model, we show by footprinting with DNase I and permanganate that nearly all sequences between the enhancer-like distal sequence element and the initiation site are protected during interphase whereas the upstream half of the U2 snRNA coding region is exposed. We also show by chromatin immunoprecipitation that the SNAPc complex, which binds the TATA-like proximal sequence element, is removed at metaphase but remains bound under conditions that induce locus-specific metaphase fragility of the U2 genes, such as loss of CSB, BRCA1, or BRCA2 function, treatment with actinomycin D, or overexpression of the tetrameric p53 C terminus. We propose that the U2 snRNA promoter establishes a persistently open state to facilitate rapid reinitiation and perhaps also to bypass TFIIH-dependent promoter melting; this open state would then be disassembled to allow metaphase chromatin condensation.

Published ahead of print on 31 March 2008.

Present address: Molecular Virology Program, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106.