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A sequence-specific core promoter-binding transcription factor recruits TRF2 to coordinately transcribe ribosomal protein genes.

ABSTRACT: Ribosomal protein (RP) genes must be coordinately expressed for proper assembly of the ribosome yet the mechanisms that control expression of RP genes in metazoans are poorly understood. Recently, TATA-binding protein-related factor 2 (TRF2) rather than the TATA-binding protein (TBP) was found to function in transcription of RP genes in Drosophila. Unlike TBP, TRF2 lacks sequence-specific DNA binding activity, so the mechanism by which TRF2 is recruited to promoters is unclear. We show that the transcription factor M1BP, which associates with the core promoter region, activates transcription of RP genes. Moreover, M1BP directly interacts with TRF2 to recruit it to the RP gene promoter. High resolution ChIP-exo was used to analyze in vivo the association of M1BP, TRF2 and TFIID subunit, TAF1. Despite recent work suggesting that TFIID does not associate with RP genes in Drosophila, we find that TAF1 is present at RP gene promoters and that its interaction might also be directed by M1BP. Although M1BP associates with thousands of genes, its colocalization with TRF2 is largely restricted to RP genes, suggesting that this combination is key to coordinately regulating transcription of the majority of RP genes in Drosophila.

SUBMITTER: Baumann DG

PROVIDER: S-EPMC5737516 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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A sequence-specific core promoter-binding transcription factor recruits TRF2 to coordinately transcribe ribosomal protein genes.

Baumann Douglas G DG Gilmour David S DS

Nucleic acids research 20171001 18

Ribosomal protein (RP) genes must be coordinately expressed for proper assembly of the ribosome yet the mechanisms that control expression of RP genes in metazoans are poorly understood. Recently, TATA-binding protein-related factor 2 (TRF2) rather than the TATA-binding protein (TBP) was found to function in transcription of RP genes in Drosophila. Unlike TBP, TRF2 lacks sequence-specific DNA binding activity, so the mechanism by which TRF2 is recruited to promoters is unclear. We show that the ...[more]

PMID: 28977400

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Project description:The motif ACTAYRNNNCCCR (Y being C or T, R being A or G, and N any nucleotide), called M4, was discovered as a putative cis-regulatory element, present 520 times in human promoter regions. Of these, 317 (61 %) are conserved within promoter sequences of four related organisms: human, mouse, rat, and dog. Recent genome-wide studies have described M4 as a transcription factor (TF) binding site for THAP11 that does often overlap with SBS (STAF Binding Site) a second core-promoter associated TF binding module, which associates with the TFs STAF/ZNF143 and RBP-J. Human M4-promoter genes show enhanced expression in cells of hematopoietic origin, especially in B lymphoblasts and peripheral blood B and T cells. Apart from RBP-J that is well known to recruit ICN1 (the intracellular transcriptional mediator of activated Notch1), the functional role of the hyperconserved M4 cis-element in the context of transcriptional regulation of M4-genes in lymphoid cells remains poorly defined.Here, we present a quantitative proteomic investigation of the M4 motif TF binding landscape in lymphoid cell lines that is further validated by ChIP experiments and functional assays. Our data strongly suggest that THAP11 and Ikaros interact directly, while NFKB1 (NF-kappa B p50) and HCF-1 are binding indirectly to M4-promoters in vitro and in living cells. Further analysis reveals that M4 is a bipartite composite cis-element, which is recognized by THAP11 via binding to the ACTAYR sequence module, thereby promoting ternary complex formation with HCF-1. Similarly, Ikaros binds to the CCCR module of the M4 motif and this interaction is crucial for recruiting NFKB1 to M4 harboring genes. Transient reporter assays in HEK293 and loss-of-function experiments in Molt4 T cells unequivocally demonstrate that binding of Ikaros and/or THAP11 to M4 bearing promoters is functionally important and therefore biologically relevant. Accordingly, this study validates our SILAC-based DNA protein interaction screening methodology as a valuable surrogate for a bona fide reverse ChIP technology.The M4 motif (ACTAYRNNNCCCR) is a functional regulatory bipartite cis-element, which engages a THAP11/HCF-1 complex via binding to the ACTAYR module, while the CCCRRNRNRC subsequence part constitutes a binding platform for Ikaros and NFKB1.

Dataset Information

A sequence-specific core promoter-binding transcription factor recruits TRF2 to coordinately transcribe ribosomal protein genes.

Publications

A sequence-specific core promoter-binding transcription factor recruits TRF2 to coordinately transcribe ribosomal protein genes.

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