Project Details
Projekt
Sperm histone code and epigenetic-mediated subfertility
Applicant
Professor Dr. Klaus Steger
Subject Area
Reproductive Medicine, Urology
Term
from 2008 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 34016037
It is now generally accepted that a sperm-specific epigenetic code is established during spermiogenesis and transmitted to the oocyte. Aberrations may represent one reason for idiopathic male infertility resulting in decreased IVF/ICSI outcome. In a previous study, gene promoters associated with histone H4 acetylated at lysine 12 (H4K12ac) and also exonic sequences associated with histone H3 acetylated at lysine 9 (H3K9ac) have been identified in ejaculated spermatozoa from fertile donors and subfertile patients applying ChlP-on-chip HG18 promoter array and ENCODE array, respectively. In the present study, the following aims will be addressed: 1) To clarify whether H4K12ac-associated gene promoters colocalize with other histones, such as H3K9ac, H3K4me3 and H3K27me3, or protamine applying Re-ChIP; 2) To determine binding sequences for protamine-1 iri fertile donors and subfertile patients; 3) To analyze the methylation status of CpG dinucleotides within gene promoters of developmental genes associated with H4K12ac and protamine-1 applying pyrosequencing; 4) To analyze the possible role of H4K12ac and H3K9ac on paternal imprinted loci; 5) To analyze expression of H4K12ac-associated genes in the paternal pronucleus of mouse zygote using in-situ hybridization and immunofluorescence in combination with confocal microscopy; 6) To perform a genome-wide bioinformatic-based data comparision of own data from H4K12ac ChlP-on-chip and protamine-1 ChlPsequencing with transcriptomes from human preimplantation embryos/embryonic stem cells and data generated in bovine model providing paternal contributed candidate genes for eariy development (coop, with project 7).
DFG Programme
Clinical Research Units
Participating Persons
Dr. Agnieszka Paradowska; Professor Dr. Wolfgang Weidner
