Functional study of 14-3-3 protein epsilon (YWHAE) in keratinocytes: microarray integrating bioinformatics approaches
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Authors: Yin, Shang-Jun; Lee, Jae-Rin; Kwak, Hyunchang; Lee, Bit-Na; Han, Ji-Won; Hahn, Myong-Joon; Park, Yong-Doo; Yang, Jun-Mo
Abstract
Previously, we detected that 14-3-3 protein epsilon (YWHAE) was involved in the pathogenesis of atopic dermatitis (AD) and tyrosinase-mediated pigmentation. In this study, we aimed to identify critical factors associated with YWHAE in human keratinocytes using high-throughput screening (HTS) approaches to reveal its functions in skin. We overexpressed YWHAE in human HaCaT keratinocytes and then conducted serial HTS studies, including RNA sequencing integrated with antibody arrays and the implementation of bioinformatics algorithms. Cumulatively, these approaches identified several novel genes in keratinocytes associated with the function of YWHAE including KRT9, KRT1, KRT6C, BST2, CIB2, APH1B, ACTC1, IFI27, TUBA1A, CAPN6, UTY, MX2, and MAPK15, based on RNA sequencing data, and MAPK1, MMP2, TYK2, NOS3, and CASP3, based on antibody array data. In particular, CD37 is a unique gene that was detected and validated in all the methods applied in this study. By integrating the datasets obtained from these HTS studies and utilizing the strengths of each method, we obtained new insights into the functional role of YWHAE in skin keratinocytes. The approach used here could contribute to the clinical understanding of YWHAE-associated applications in the treatment of AD disease.
Genetic score of power-speed and endurance track and field athletes
SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS
Authors: Ben-Zaken, S.; Meckel, Y.; Nemet, D.; Eliakim, A.
Abstract
Athletic excelling capability in a specific sport results from the combined influence of hundreds of genetic polymorphisms. The aim of the current study was to characterize athletes' polygenetic scores. We developed two polygenetic scores: (a) Power Genetic Distance Score based on two polymorphisms (PGDS2; ACE(I/D), ACTN3(C/T)) or five polymorphisms (PGDS5; ACTN3(C/T), ACE(I/D), IL6(-174G/C), NOS3(T/C), AGT(MET235THR)); and (b) Endurance Genetic Distance Score based on two polymorphisms (EGDS2; ACE(I/D), ACTN3(C/T)) or five polymorphisms (EGDS5; PPARGC1A(Gly482Ser), PPARA(intron7G/C), PPARD(T294C), NRF2(A/C), HIFC/T). Eighty-two power-speed athletes, 87 endurance athletes, and 119 nonathletic controls participated in the study. Genomic DNA was extracted from peripheral blood. Power-speed athletes' mean PGDS2 (46.1) and PGDS5 (29.4) were significantly higher compared with their mean EGDS2 (36.4) and EGDS5 (23.1; P<0.05, P<0.01, respectively); and compared with controls' mean PGDS2 (36.6) and PGDS5 (24.2; P<0.05, P<0.05, respectively). Endurance athletes' mean EGDS2 (60.3) and EGDS5 (35.3) were significantly higher compared with their mean PGDS2 (26.9) and PGDS5 (21.8; P<0.001, P<0.001, respectively); and compared with controls' mean EGDS2 (51.2) and EGDS5 (26.1; P<0.05, P<0.001, respectively). We conclude that polygenetic scores can differentiate power-speed from endurance athletes. Whether these scores may be used to identify elite power-speed or endurance athletes' needs to be addressed in future studies.