PMID- 24553382 OWN - NLM STAT- MEDLINE DCOM- 20141125 LR - 20211021 IS - 1521-009X (Electronic) IS - 0090-9556 (Print) IS - 0090-9556 (Linking) VI - 42 IP - 5 DP - 2014 May TI - Inhibition of SULT4A1 expression induces up-regulation of phototransduction gene expression in 72-hour postfertilization zebrafish larvae. PG - 947-53 LID - 10.1124/dmd.114.057042 [doi] AB - Sulfotransferase (SULT) 4A1 is an orphan enzyme that shares distinct structure and sequence similarities with other cytosolic SULTs. SULT4A1 is primarily expressed in neuronal tissue and is also the most conserved SULT, having been identified in every vertebrate investigated to date. Certain haplotypes of the SULT4A1 gene are correlated with higher baseline psychopathology in schizophrenic patients, but no substrate or function for SULT4A1 has yet been identified despite its high level of sequence conservation. In this study, deep RNA sequencing was used to search for alterations in gene expression in 72-hour postfertilization zebrafish larvae following transient SULT4A1 knockdown (KD) utilizing splice blocking morpholino oligonucleotides. This study demonstrates that transient inhibition of SULT4A1 expression in developing zebrafish larvae results in the up-regulation of several genes involved in phototransduction. SULT4A1 KD was verified by immunoblot analysis and quantitative real-time polymerase chain reaction (qPCR). Gene regulation changes identified by deep RNA sequencing were validated by qPCR. This study is the first identification of a cellular process whose regulation appears to be associated with SULT4A1 expression. FAU - Crittenden, Frank AU - Crittenden F AD - Departments of Pharmacology and Toxicology (F.C., H.T., J.P., C.N.F.), Medicine (D.C.), and Vision Sciences (T.K.), University of Alabama at Birmingham, Birmingham, Alabama; and R&D Systems, Minneapolis, Minnesota (C.M.E., Z.L.W.). FAU - Thomas, Holly AU - Thomas H FAU - Ethen, Cheryl M AU - Ethen CM FAU - Wu, Zhengliang L AU - Wu ZL FAU - Chen, Dongquan AU - Chen D FAU - Kraft, Timothy W AU - Kraft TW FAU - Parant, John M AU - Parant JM FAU - Falany, Charles N AU - Falany CN LA - eng GR - R01 GM113980/GM/NIGMS NIH HHS/United States GR - R21 MH095946/MH/NIMH NIH HHS/United States GR - R21MH095946/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140219 PL - United States TA - Drug Metab Dispos JT - Drug metabolism and disposition: the biological fate of chemicals JID - 9421550 RN - 0 (Morpholinos) RN - 0 (Zebrafish Proteins) RN - 63231-63-0 (RNA) RN - EC 2.8.2.- (SULT4A1 protein, zebrafish) RN - EC 2.8.2.- (Sulfotransferases) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Brain/embryology/metabolism MH - Eye/embryology/metabolism MH - Fertilization MH - *Gene Expression Regulation, Developmental/drug effects MH - Gene Knockdown Techniques MH - Larva MH - Light Signal Transduction/*genetics MH - Molecular Sequence Data MH - Morpholinos/pharmacology MH - RNA/genetics MH - Real-Time Polymerase Chain Reaction MH - Sequence Analysis, RNA MH - Sequence Homology, Amino Acid MH - Sulfotransferases/genetics/*physiology MH - *Transcriptome MH - Up-Regulation MH - Zebrafish/embryology/*genetics MH - Zebrafish Proteins/genetics/*physiology PMC - PMC3989789 EDAT- 2014/02/21 06:00 MHDA- 2014/12/15 06:00 PMCR- 2015/05/01 CRDT- 2014/02/21 06:00 PHST- 2014/02/21 06:00 [entrez] PHST- 2014/02/21 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] PHST- 2015/05/01 00:00 [pmc-release] AID - dmd.114.057042 [pii] AID - DMD_057042 [pii] AID - 10.1124/dmd.114.057042 [doi] PST - ppublish SO - Drug Metab Dispos. 2014 May;42(5):947-53. doi: 10.1124/dmd.114.057042. Epub 2014 Feb 19.