@article {69421, title = {YAP condensates are highly organized hubs}, journal = {iScience}, year = {2024}, month = {2024 May 07}, pages = {109927}, abstract = {

YAP/TEAD signaling is essential for organismal development, cell proliferation, and cancer progression. As a transcriptional coactivator, how YAP activates its downstream target genes is incompletely understood. YAP forms biomolecular condensates in response to hyperosmotic stress, concentrating transcription-related factors to activate downstream target genes. However, whether YAP forms condensates under other signals, how YAP condensates organize and function, and how YAP condensates activate transcription in general are unknown. Here, we report that endogenous YAP forms sub-micron scale condensates in response to Hippo pathway regulation and actin cytoskeletal tension. YAP condensates are stabilized by the transcription factor TEAD1, and recruit BRD4, a coactivator that is enriched at active enhancers. Using single-particle tracking, we found that YAP condensates slowed YAP diffusion within condensate boundaries, a possible mechanism for promoting YAP target search. These results reveal that YAP condensate formation is a highly regulated process that is critical for YAP/TEAD target gene expression.

}, issn = {2589-0042}, doi = {https://doi.org/10.1016/j.isci.2024.109927}, url = {https://www.sciencedirect.com/science/article/pii/S2589004224011490}, author = {Siyuan Hao and Ye Jin Lee and Nadav Benhamou Goldfajn and Eduardo Flores and Jindayi Liang and Hannah Fuehrer and Justin Demmerle and Jennifer Lippincott-Schwartz and Zhe Liu and Shahar Sukenik and Danfeng Cai} } @article {67646, title = {YAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion.}, journal = {Nature Communications}, volume = {12}, year = {2021}, month = {2021 Jul 23}, pages = {4502}, abstract = {

Cells in many tissues, such as bone, muscle, and placenta, fuse into syncytia to acquire new functions and transcriptional programs. While it is known that fused cells are specialized, it is unclear whether cell-fusion itself contributes to programmatic-changes that generate the new cellular state. Here, we address this by employing a fusogen-mediated, cell-fusion system to create syncytia from undifferentiated cells.\ RNA-Seq analysis reveals VSV-G-induced cell fusion precedes transcriptional changes. To gain mechanistic insights, we measure the plasma membrane surface area after cell-fusion and observe it diminishes through increases in endocytosis. Consequently, glucose transporters internalize, and cytoplasmic glucose and ATP transiently decrease. This reduced energetic state activates AMPK, which inhibits YAP1, causing transcriptional-reprogramming and cell-cycle arrest. Impairing either endocytosis or AMPK activity prevents YAP1 inhibition and cell-cycle arrest after fusion. Together, these data demonstrate plasma membrane diminishment upon cell-fusion causes transient nutrient stress that may promote transcriptional-reprogramming independent from extrinsic cues.

}, issn = {2041-1723}, doi = {10.1038/s41467-021-24708-2}, author = {Feliciano, Daniel and Ott, Carolyn M and Isabel Espinosa Medina and Weigel, Aubrey V and Benedetti, Lorena and Milano, Kristin M and Tang, Zhonghua and Lee, Tzumin and Kliman, Harvey J and Guller, Seth M and Lippincott-Schwartz, Jennifer} } @article {65229, title = {The yellow gene influences Drosophila male mating success through sex comb melanization.}, journal = {eLife}, volume = {8}, year = {2019}, month = {2019 Oct 15}, abstract = {

males perform a series of courtship behaviors that, when successful, result in copulation with a female. For over a century, mutations in the gene, named for its effects on pigmentation, have been known to reduce male mating success. Prior work has suggested that influences mating behavior through effects on wing extension, song, and/or courtship vigor. Here, we rule out these explanations, as well as effects on the nervous system more generally, and find instead that the effects of on male mating success are mediated by its effects on pigmentation of male-specific leg structures called sex combs. Loss of expression in these modified bristles reduces their melanization, which changes their structure and causes difficulty grasping females prior to copulation. These data illustrate why the mechanical properties of anatomy, not just neural circuitry, must be considered to fully understand the development and evolution of behavior.

}, issn = {2050-084X}, doi = {10.7554/eLife.49388}, author = {Massey, Jonathan H and Chung, Daayun and Siwanowicz, Igor and Stern, David L and Wittkopp, Patricia J} } @article {46645, title = {Y do we drink?}, journal = {Cell}, volume = {95}, year = {1998}, month = {1998 Dec 11}, pages = {733-5}, keywords = {Alcohol Drinking, Alcoholic Intoxication, Animals, Ethanol, Feeding Behavior, Humans, Mice, Mice, Mutant Strains, Neuropeptide Y, Rats}, issn = {0092-8674}, author = {Tecott, L H and Heberlein, U} } @article {960, title = {Yan functions as a general inhibitor of differentiation and is negatively regulated by activation of the Ras1/MAPK pathway.}, journal = {Cell}, volume = {81}, year = {1995}, month = {1995 Jun 16}, pages = {857-66}, abstract = {

Drosophila yan has been postulated to act as an antagonist of the proneural signal mediated by the sevenless/Ras1/MAPK pathway. We have mutagenized the eight MAPK phosphorylation consensus sites of yan and examined the effects of overexpressing the mutant protein in transgenic flies and transfected S2 cultured cells. Our results suggest that phosphorylation by MAPK affects the stability and subcellular localization of yan, resulting in rapid down-regulation of yan activity. Furthermore, MAPK-mediated down-regulation of yan function appears to be critical for the proper differentiation of both neuronal and nonneuronal tissues throughout development, suggesting that yan is an essential component of a general timing mechanism controlling the competence of a cell to respond to inductive signals.

}, keywords = {Alleles, Animals, Binding Sites, Calcium-Calmodulin-Dependent Protein Kinases, Developmental, DNA-Binding Proteins, Down-Regulation, Drosophila, Drosophila Proteins, Eye, Eye Proteins, Gene Expression Regulation, GTP-Binding Proteins, Membrane Glycoproteins, Mutagenesis, Neurons, Phosphorylation, Receptor Protein-Tyrosine Kinases, Repressor Proteins, Signal Transduction, Site-Directed}, issn = {0092-8674}, doi = {10.1186/gb-2007-8-7-r145}, author = {Rebay, I and Rubin, G M} } @article {1176, title = {Yeast mitochondrial RNA polymerase is homologous to those encoded by bacteriophages T3 and T7.}, journal = {Cell}, volume = {51}, year = {1987}, month = {1987 Oct 9}, pages = {89-99}, abstract = {

Analysis of the nucleotide sequence of the genetic locus for yeast mitochondrial RNA polymerase (RPO41) reveals a continuous open reading frame with the coding potential for a polypeptide of 1351 amino acids, a size consistent with the electrophoretic mobility of this enzymatic activity. The transcription product from this gene spans the singular reading frame. In vivo transcript abundance reflects codon usage and growth under stringent conditions for mitochondrial biogenesis and function results in a several fold higher level of gene expression than growth under glucose repression. A comparison of the yeast mitochondrial RNA polymerase amino acid sequence to those of E. coli RNA polymerase subunits failed to demonstrate any regions of homology. Interestingly, the mitochondrial enzyme is highly homologous to the DNA-directed RNA polymerases of bacteriophages T3 and T7, especially in regions most highly conserved between the T3 and T7 enzymes themselves.

}, keywords = {Amino Acid Sequence, Base Sequence, DNA, DNA-Directed RNA Polymerases, Escherichia coli, Genetic, Mitochondria, Molecular Sequence Data, Nucleic Acid, Saccharomyces cerevisiae, Sequence Homology, T-Phages, Transcription}, issn = {0092-8674}, doi = {10.1101/gad.1352105}, author = {Masters, B S and Stohl, L L and Clayton, D A} }