ArticlePLoS genetics2014
Drosophila melanogaster Hox transcription factors access the RNA polymerase II machinery through direct homeodomain binding to a conserved motif of mediator subunit Med19.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- The Mediator Complex: From Transcriptional Regulation to Disease Pathogenesis.International journal of molecular sciences · 2026Review
- Novel Antennapedia and Ultrabithorax trimeric complexes with TBP and Exd regulate transcription.Hereditas · 2024Article
- Trimeric complexes of Antp-TBP with TFIIEβ or Exd modulate transcriptional activity.Hereditas · 2022Article
- The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II.Nucleic acids research · 2022Article
- Transcriptional Regulation and Implications for ControllingJournal of developmental biology · 2022Review
- Article
- Cell-type-specific Hox regulatory strategies orchestrate tissue identity.Current biology : CB · 2021Article
- The role of mediator complex subunit 19 in human diseases.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Mediator Complex Subunit 19 Promotes the Development of Hepatocellular Carcinoma by Regulating the AKT/mTOR Signaling Pathway.Frontiers in oncology · 2021Article
- Mediator complex subunit Med19 binds directly GATA transcription factors and is required with Med1 for GATA-driven gene regulationThe Journal of biological chemistry · 2020Article
- HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol.Frontiers in genetics · 2020Article
- Article
- A high-throughput method to identify trans-activation domains within transcription factor sequences.The EMBO journal · 2018Article
- Article
- Knockdown of mediator subunit Med19 suppresses bladder cancer cell proliferation and migration by downregulating Wnt/β-catenin signalling pathway.Journal of cellular and molecular medicine · 2017Article
- The Hox proteins Ubx and AbdA collaborate with the transcription pausing factor M1BP to regulate gene transcription.The EMBO journal · 2017Article
- Controlling the Master: Chromatin Dynamics at the MYC Promoter Integrate Developmental Signaling.Genes · 2017Review
- Regulatory Enhancer-Core-Promoter Communication via Transcription Factors and Cofactors.Trends in genetics : TIG · 2016Review
- Defining the essential function of FBP/KSRP proteins: Drosophila Psi interacts with the mediator complex to modulate MYC transcription and tissue growth.Nucleic acids research · 2016Article
- Homeodomain proteins: an update.Chromosoma · 2016Review
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hox genes in species across the metazoa encode transcription factors (TFs) containing highly-conserved homeodomains that bind target DNA sequences to regulate batteries of developmental target genes. DNA-bound Hox proteins, together with other TF partners, induce an appropriate transcriptional response by RNA Polymerase II (PolII) and its associated general transcription factors. How the evolutionarily conserved Hox TFs interface with this general machinery to generate finely regulated transcriptional responses remains obscure. One major component of the PolII machinery, the Mediator (MED) transcription complex, is composed of roughly 30 protein subunits organized in modules that bridge the PolII enzyme to DNA-bound TFs. Here, we investigate the physical and functional interplay between Drosophila melanogaster Hox developmental TFs and MED complex proteins. We find that the Med19 subunit directly binds Hox homeodomains, in vitro and in vivo. Loss-of-function Med19 mutations act as dose-sensitive genetic modifiers that synergistically modulate Hox-directed developmental outcomes. Using clonal analysis, we identify a role for Med19 in Hox-dependent target gene activation. We identify a conserved, animal-specific motif that is required for Med19 homeodomain binding, and for activation of a specific Ultrabithorax target. These results provide the first direct molecular link between Hox homeodomain proteins and the general PolII machinery. They support a role for Med19 as a PolII holoenzyme-embedded "co-factor" that acts together with Hox proteins through their homeodomains in regulated developmental transcription.
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