학술논문

Functionally distinct promoter classes initiate transcription via different mechanisms reflected in focused versus dispersed initiation patterns.
Document Type
Article
Source
EMBO Journal. May2023, Vol. 42 Issue 10, p1-24. 24p.
Subject
*RNA polymerase II
*RNA polymerases
*DROSOPHILA melanogaster
*TRANSGENIC organisms
*TRANSCRIPTION factors
Language
ISSN
0261-4189
Abstract
Recruitment of RNA polymerase II (Pol II) to promoters is essential for transcription. Despite conflicting evidence, the Pol II preinitiation complex (PIC) is often thought to have a uniform composition and to assemble at all promoters via an identical mechanism. Here, using Drosophila melanogaster S2 cells as a model, we demonstrate that different promoter classes function via distinct PICs. Promoter DNA of developmentally regulated genes readily associates with the canonical Pol II PIC, whereas housekeeping promoters do not, and instead recruit other factors such as DREF. Consistently, TBP and DREF are differentially required by distinct promoter types. TBP and its paralog TRF2 also function at different promoter types in a partially redundant manner. In contrast, TFIIA is required at all promoters, and we identify factors that can recruit and/or stabilize TFIIA at housekeeping promoters and activate transcription. Promoter activation by tethering these factors is sufficient to induce the dispersed transcription initiation patterns characteristic of housekeeping promoters. Thus, different promoter classes utilize distinct mechanisms of transcription initiation, which translate into different focused versus dispersed initiation patterns. Synopsis: Functionally distinct promoter types are characterized by preferential responsiveness to specific activators and different transcription initiation patterns. This study demonstrates distinct transcription factor requirements and transcription initiation mechanisms at housekeeping vs developmental gene promoters, which translate into dispersed versus focused transcription initiation patterns.Developmental but not housekeeping core promoter DNA is sufficient to assemble RNA polymerase II preinitiation complexes (PICs) in vitro.The transcription factor TBP is required for transcription at a subset of developmental promoters, while TFIIA is required at all promoters.The TBP paralog TRF2 is required for transcription at a subset of developmental and housekeeping promoters and is partially redundant with TBP.Recruitment of housekeeping or developmental coactivators to minimal promoters is sufficient to reproduce endogenous transcription initiation patterns. [ABSTRACT FROM AUTHOR]