| 2002 |
Leo1 (along with Ctr9 and Rtf1) is a component of the Paf1/RNA Polymerase II complex in S. cerevisiae, distinct from the Srb-mediator form of Pol II holoenzyme. Deletion of LEO1 suppresses many paf1Δ phenotypes (e.g., restores CLN1 expression), indicating Leo1 participates in the same functional complex as Paf1. |
Tandem affinity purification, mass spectrometry, genetic epistasis (double-mutant analysis) |
Molecular and cellular biology |
High |
11884586
|
| 2010 |
The Leo1 subunit of the yeast Paf1 complex directly binds RNA in vitro. In vivo RNA-IP showed that Leo1, but not Rtf1, is necessary for Paf1C to associate with RNA. Cells lacking Leo1 show reduced Paf1C recruitment to transcribed chromatin and decreased levels of histone H3 and H3K4me3, suggesting Leo1-RNA interaction stabilizes complex localization at actively transcribed regions to influence chromatin structure. |
In vitro RNA-binding assay with purified protein, RNA immunoprecipitation (RNA-IP) in vivo, ChIP |
The Journal of biological chemistry |
High |
20732871
|
| 2015 |
In fission yeast, the Leo1-Paf1 subcomplex of Paf1C is required to prevent heterochromatin spreading into euchromatin. Deletion of Leo1 decreases nucleosome turnover at heterochromatin boundary regions, leading to stabilization of heterochromatin (increased H3K9me2), in an RNAi-independent manner. |
Genome-wide ChIP-exo for H3K9me2, random mutant screen, nucleosome turnover assays |
EMBO reports |
High |
26518661
|
| 2010 |
In zebrafish, Leo1 is a nuclear protein; a mutant Leo1 lacking the nuclear localization signal is redistributed to the cytoplasm and causes defects in cardiomyocyte differentiation at the atrioventricular boundary and loss of neural crest cell populations, establishing a functional requirement for nuclear Leo1 in vertebrate development. |
Genetic screen, identification of loss-of-function mutant, subcellular localization (nuclear vs. cytoplasmic distribution), phenotypic analysis of cardiac and neural crest markers |
Developmental biology |
Medium |
20178782
|
| 2014 |
In AML cells, PRL-3 (an oncogenic phosphatase) upregulates LEO1 expression by increasing JMJD2C histone demethylase occupancy on the LEO1 promoter, thereby reducing H3K9me3 repressive marks. LEO1 in turn stabilizes the PAF complex and maintains expression of SOX2 and SOX4 oncogenes; loss of LEO1 destabilizes the PAF complex and reverses PRL-3 oncogenic phenotypes. |
SILAC-based quantitative proteomics, ChIP for histone marks and JMJD2C, LEO1 knockdown/overexpression, PAF complex co-immunoprecipitation |
Cancer research |
Medium |
24686170
|
| 2017 |
In Drosophila, the PAF1 complex component Leo1 physically interacts with Myc and helps recruit Myc to target gene promoters. Because PAF1C is associated with active genes, Leo1 contributes to Myc targeting to open chromatin/active promoters. |
Co-immunoprecipitation / physical interaction assays, ChIP for Myc binding at target promoters with and without Leo1 |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
29078288
|
| 2023 |
CDK12 phosphorylates LEO1 (identified by chemical genetic and phosphoproteomic screening). Acute depletion of LEO1 or substitution of its CDK12 phosphorylation sites with alanine attenuates PAF1C association with elongating RNA Pol II and impairs processive transcription elongation. LEO1 is also dephosphorylated by the Integrator-PP2A complex (INTAC); depletion of INTAC promotes PAF1C–Pol II association, revealing antagonistic regulation of LEO1 phosphorylation by CDK12 and INTAC. |
Chemical genetic CDK12 inhibition, phosphoproteomic mass spectrometry, alanine-substitution mutagenesis, co-immunoprecipitation of PAF1C with Pol II, nascent transcription elongation assays |
Science advances |
High |
37205756
|
| 2021 |
LEO1 directly interacts with Cockayne syndrome protein B (CSB/ERCC6) in vitro and co-exists in a common complex in human cells. Both proteins are recruited to sites of DNA damage. Following UVC or cisplatin treatment, LEO1 and CSB show a transcription-dependent, coordinated association with chromatin. LEO1 knockdown reduces CSB chromatin recruitment, increases UV/cisplatin sensitivity, impairs RNA synthesis recovery, and slows cyclobutane pyrimidine dimer excision; CSB absence similarly reduces LEO1 chromatin recruitment, indicating reciprocal functional dependence in transcription-coupled DNA repair. |
Yeast two-hybrid screening, in vitro direct interaction with purified recombinant proteins, co-immunoprecipitation in human cells, fluorescent recruitment to laser-induced DNA damage sites, cell fractionation (chromatin association), LEO1 knockdown/knockout functional assays (RNA synthesis recovery, CPD excision, clonogenic survival) |
Nucleic acids research |
High |
34096589
|