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1.
Nat Plants ; 7(9): 1213-1219, 2021 09.
Article in English | MEDLINE | ID: mdl-34354260

ABSTRACT

To compensate for a sessile nature, plants have developed sophisticated mechanisms to sense varying environmental conditions. Phytochromes (phys) are light and temperature sensors that regulate downstream genes to render plants responsive to environmental stimuli1-4. Here, we show that phyB directly triggers the formation of a repressive chromatin loop by physically interacting with VERNALIZATION INSENSITIVE 3-LIKE1/VERNALIZATION 5 (VIL1/VRN5), a component of Polycomb Repressive Complex 2 (PRC2)5,6, in a light-dependent manner. VIL1 and phyB cooperatively contribute to the repression of growth-promoting genes through the enrichment of Histone H3 Lys27 trimethylation (H3K27me3), a repressive histone modification. In addition, phyB and VIL1 mediate the formation of a chromatin loop to facilitate the repression of ATHB2. Our findings show that phyB directly utilizes chromatin remodelling to regulate the expression of target genes in a light-dependent manner.


Subject(s)
Acclimatization/genetics , Adaptation, Ocular/genetics , Chromatin Assembly and Disassembly/genetics , Homeodomain Proteins/metabolism , Phytochrome B/metabolism , Polycomb-Group Proteins/metabolism , Stress, Physiological/genetics , Arabidopsis/genetics , Chromatin Assembly and Disassembly/physiology , Gene Expression Regulation, Plant , Genes, Plant , Genetic Variation , Genotype , Homeodomain Proteins/genetics , Mutation , PHD Zinc Fingers/genetics , PHD Zinc Fingers/physiology , Phytochrome B/genetics , Polycomb-Group Proteins/genetics , Stress, Physiological/physiology
2.
Biochemistry ; 59(4): 389-399, 2020 02 04.
Article in English | MEDLINE | ID: mdl-31746185

ABSTRACT

Transcription factor 19 (TCF19) plays critical roles in type 1 diabetes and the maintenance of pancreatic ß cells. Recent studies have also implicated TCF19 in cell proliferation of hepatic carcinoma and non-small cell lung carcinoma; however, the mechanism underlying this regulation remains elusive. At the molecular level, TCF19 contains two modules, the plant homeodomain (PHD) finger and the forkhead-associated (FHA) domain, of unclear function. Here, we show that TCF19 mediates hepatocellular carcinoma HepG2 cell proliferation through its PHD finger that recognizes trimethylated lysine 4 of histone 3 (H3K4me3). W316 of the PHD finger of TCF19 is one of the critical residues eliciting this function. Whole genome microarray analysis and orthogonal cell-based assays identified a large subset of genes involved in cell survival and proliferation that depend on TCF19. Our data suggest that TCF19 acts as a pro-oncogene in hepatocellular carcinoma cells and that its functional PHD finger is critical in cell proliferation.


Subject(s)
Histones/metabolism , Transcription Factors/metabolism , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Proliferation/physiology , DNA-Binding Proteins/metabolism , Hep G2 Cells , Histone Code , Histones/genetics , Humans , Liver Neoplasms/metabolism , Lysine/metabolism , Methylation , Models, Molecular , PHD Zinc Fingers/physiology , Protein Binding , Transcription Factors/physiology
3.
Nat Commun ; 10(1): 2314, 2019 05 24.
Article in English | MEDLINE | ID: mdl-31127101

ABSTRACT

Histone methyltransferase MLL4 is centrally involved in transcriptional regulation and is often mutated in human diseases, including cancer and developmental disorders. MLL4 contains a catalytic SET domain that mono-methylates histone H3K4 and seven PHD fingers of unclear function. Here, we identify the PHD6 finger of MLL4 (MLL4-PHD6) as a selective reader of the epigenetic modification H4K16ac. The solution NMR structure of MLL4-PHD6 in complex with a H4K16ac peptide along with binding and mutational analyses reveal unique mechanistic features underlying recognition of H4K16ac. Genomic studies show that one third of MLL4 chromatin binding sites overlap with H4K16ac-enriched regions in vivo and that MLL4 occupancy in a set of genomic targets depends on the acetyltransferase activity of MOF, a H4K16ac-specific acetyltransferase. The recognition of H4K16ac is conserved in the PHD7 finger of paralogous MLL3. Together, our findings reveal a previously uncharacterized acetyllysine reader and suggest that selective targeting of H4K16ac by MLL4 provides a direct functional link between MLL4, MOF and H4K16 acetylation.


Subject(s)
DNA-Binding Proteins/metabolism , Histone Acetyltransferases/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Histones/metabolism , PHD Zinc Fingers/physiology , Acetylation , Animals , Binding Sites , Chromatin/metabolism , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , DNA-Binding Proteins/isolation & purification , Gene Knockout Techniques , HEK293 Cells , Histone Acetyltransferases/genetics , Histone-Lysine N-Methyltransferase/chemistry , Histones/chemistry , Humans , Mice, Transgenic , Models, Molecular , Mutagenesis, Site-Directed , Nuclear Magnetic Resonance, Biomolecular , Protein Processing, Post-Translational/physiology , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism
4.
Plant Signal Behav ; 12(5): e1308619, 2017 05 04.
Article in English | MEDLINE | ID: mdl-28498016

ABSTRACT

Vernalization is a response to the winter cold to acquire the competence to flower in next spring. VERNALIZATION INSENSITIVE 3 (VIN3) is a PHD-finger protein that binds to modified histones in vitro. VIN3 is induced by long-term cold and is necessary for Polycomb Repression Complex 2 (PRC2)-mediated tri-methylation of Histone H3 Lysine 27 (H3K27me3) at the FLC locus in Arabidopsis. An alteration in the PHD-finger domain of VIN3 changes the binding specificity of the PHD-finger domain of VIN3 in vitro and results in an accelerated vernalization response in vivo. The acceleration in vernalization response is achieved by increased enrichments of VIN3 and tri-methylation of Histone H3 Lysine 27 (H3K27me3) at the FLC locus without invoking the increased enrichment of Polycomb Repressive Complex 2. This result indicates that the binding specificity of the PHD-finger domain of VIN3 plays a role in mediating a proper vernalization response in Arabidopsis. Furthermore, this work shows a potential that the alteration of PHD-finger domains could be applied to alter various developmental processes in plants.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Arabidopsis/genetics , Arabidopsis/physiology , Arabidopsis Proteins/genetics , Chromatin/genetics , Chromatin/metabolism , Flowers/genetics , Flowers/metabolism , PHD Zinc Fingers/genetics , PHD Zinc Fingers/physiology , Polycomb Repressive Complex 2/genetics , Polycomb Repressive Complex 2/metabolism
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