XGlobal regulation of promoter melting in naive lymphocytes

Fedor Kouzine, Damian Wojtowicz, Arito Yamane, Wolfgang Resch, Kyong Rim Kieffer-Kwon, Russell Bandle, Steevenson Nelson, Hirotaka Nakahashi, Parirokh Awasthi, Lionel Feigenbaum, Herve Menoni, Jan Hoeijmakers, Wim Vermeulen, Hui Ge, Teresa M. Przytycka, David Levens, Rafael Casellas

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

125 Citaten (Scopus)

Samenvatting

Lymphocyte activation is initiated by a global increase in messenger RNA synthesis. However, the mechanisms driving transcriptome amplification during the immune response are unknown. By monitoring single-stranded DNA genome wide, we show that the genome of naive cells is poised for rapid activation. In G 0, ∼90% of promoters from genes to be expressed in cycling lymphocytes are polymerase loaded but unmelted and support only basal transcription. Furthermore, the transition from abortive to productive elongation is kinetically limiting, causing polymerases to accumulate nearer to transcription start sites. Resting lymphocytes also limit the expression of the transcription factor IIH complex, including XPB and XPD helicases involved in promoter melting and open complex extension. To date, two rate-limiting steps have been shown to control global gene expression in eukaryotes: preinitiation complex assembly and polymerase pausing. Our studies identify promoter melting as a third key regulatory step and propose that this mechanism ensures a prompt lymphocyte response to invading pathogens.

Originele taal-2Engels
Pagina's (van-tot)988
Aantal pagina's1
TijdschriftCell
Volume153
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - 23 mei 2013
Extern gepubliceerdJa

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