@article{RonquilloHankeGogokhiaReveloetal.2016,
  author    = {Ronquillo, Cecinio C. and Hanke-Gogokhia, Christin and Revelo, Monica P. and Frederick, Jeanne M. and Jiang, Li and Baehr, Wolfgang},
  title     = {Ciliopathy-associated IQCB1/NPHP5 protein is required for mouse photoreceptor outer segment formation},
  series = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology},
  volume    = {30},
  journal   = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology},
  publisher = {Federation of American Societies for Experimental Biology},
  address   = {Bethesda},
  issn      = {0892-6638},
  doi       = {10.1096/fj.201600511R},
  pages     = {3400 -- 3412},
  year      = {2016},
  abstract  = {Null mutations in the human IQCB1/NPHP5 (nephrocystin-5) gene that encodes NPHP5 are the most frequent cause of Senior-LOken syndrome, a ciliopathy that is characterized by Leber congenital amaurosis and nephronophthisis. We generated germline Nphp5-knockout mice by placing a -Geo gene trap in intron 4, thereby truncating NPHP5 at Leu87 and removing all known functional domains. At eye opening, Nphp5(-/-) mice exhibited absence of scotopic and photopic electroretinogram responses, a phenotype that resembles Leber congenital amaurosis. Outer segment transmembrane protein accumulation in Nphp5(-/-) endoplasmic reticulum was evident as early as postnatal day (P)6. EGFP-CETN2, a centrosome and transition zone marker, identified basal bodies in Nphp5(-/-) photoreceptors, but without fully developed transition zones. Ultrastructure of P6 and 10 Nphp5(-/-) photoreceptors revealed aberrant transition zones of reduced diameter. Nphp5(-/-) photoreceptor degeneration was complete at 1 mo of age but was delayed significantly in Nphp5(-/-);Nrl(-/-) (cone only) retina. Nphp5(-/-) mouse embryonic fibroblast developed normal cilia, and Nphp5(-/-) kidney histology at 1 yr of age showed no significant pathology. Results establish that nephrocystin-5 is essential for photoreceptor outer segment formation but is dispensable for kidney and mouse embryonic fibroblast ciliary formation.},
  language  = {en}
}
@article{KappelFriedrichOberkofleretal.2023,
  author    = {Kappel, Christian and Friedrich, Thomas and Oberkofler, Vicky and Jiang, Li and Crawford, Tim and Lenhard, Michael and B{\"a}urle, Isabel},
  title     = {Genomic and epigenomic determinants of heat stress-induced transcriptional memory in Arabidopsis},
  series = {Genome biology : biology for the post-genomic era},
  volume    = {24},
  journal   = {Genome biology : biology for the post-genomic era},
  number    = {1},
  publisher = {BioMed Central},
  address   = {London},
  issn      = {1474-760X},
  doi       = {10.1186/s13059-023-02970-5},
  pages     = {23},
  year      = {2023},
  abstract  = {Background Transcriptional regulation is a key aspect of environmental stress responses. Heat stress induces transcriptional memory, i.e., sustained induction or enhanced re-induction of transcription, that allows plants to respond more efficiently to a recurrent HS. In light of more frequent temperature extremes due to climate change, improving heat tolerance in crop plants is an important breeding goal. However, not all heat stress-inducible genes show transcriptional memory, and it is unclear what distinguishes memory from non-memory genes. To address this issue and understand the genome and epigenome architecture of transcriptional memory after heat stress, we identify the global target genes of two key memory heat shock transcription factors, HSFA2 and HSFA3, using time course ChIP-seq. Results HSFA2 and HSFA3 show near identical binding patterns. In vitro and in vivo binding strength is highly correlated, indicating the importance of DNA sequence elements. In particular, genes with transcriptional memory are strongly enriched for a tripartite heat shock element, and are hallmarked by several features: low expression levels in the absence of heat stress, accessible chromatin environment, and heat stress-induced enrichment of H3K4 trimethylation. These results are confirmed by an orthogonal transcriptomic data set using both de novo clustering and an established definition of memory genes. Conclusions Our findings provide an integrated view of HSF-dependent transcriptional memory and shed light on its sequence and chromatin determinants, enabling the prediction and engineering of genes with transcriptional memory behavior.},
  language  = {en}
}
@article{ZhangHankeGogokhiaJiangetal.2015,
  author    = {Zhang, Houbin and Hanke-Gogokhia, Christin and Jiang, Li and Li, Xiaobo and Wang, Pu and Gerstner, Cecilia D. and Frederick, Jeanne M. and Yang, Zhenglin and Baehr, Wolfgang},
  title     = {Mistrafficking of prenylated proteins causes retinitis pigmentosa 2},
  series = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology},
  volume    = {29},
  journal   = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology},
  number    = {3},
  publisher = {Federation of American Societies for Experimental Biology},
  address   = {Bethesda},
  issn      = {0892-6638},
  doi       = {10.1096/fj.14-257915},
  pages     = {932 -- 942},
  year      = {2015},
  abstract  = {The retinitis pigmentosa 2 polypeptide (RP2) functions as a GTPase-activating protein (GAP) for ARL3 (Arf-like protein 3), a small GTPase. ARL3 is an effector of phosphodiesterase 6 Delta (PDE6D), a prenyl-binding protein and chaperone of prenylated protein in photoreceptors. Mutations in the human RP2 gene cause X-linked retinitis pigmentosa (XLRP) and cone-rod dystrophy (XL-CORD). To study mechanisms causing XLRP, we generated an RP2 knockout mouse. The RP2h(-/-) mice exhibited a slowly progressing rod-cone dystrophy simulating the human disease. RP2h(-/-) scotopic a-wave and photopic b-wave amplitudes declined at 1 mo of age and continued to decline over the next 6 mo. Prenylated PDE6 subunits and G-protein coupled receptor kinase 1 (GRK1) were unable to traffic effectively to the RP2h(-/-) outer segments. Mechanistically, absence of RP2 GAP activity increases ARL3-GTP levels, forcing PDE6D to assume a predominantly "closed" conformation that impedes binding of lipids. Lack of interaction disrupts trafficking of PDE6 and GRK1 to their destination, the photoreceptor outer segments. We propose that hyperactivity of ARL3-GTP in RP2 knockout mice and human patients with RP2 null alleles leads to XLRP resembling recessive rod-cone dystrophy.},
  language  = {en}
}