title: Nuclease Footprints in Sperm Project Past and Future Chromatin Regulatory Events.
abstract: Nuclear remodeling to a condensed state is a hallmark of spermatogenesis. This is achieved by replacement of histones with protamines. Regions retaining nucleosomes may be of functional significance. To determine their potential roles, sperm from wild type and transgenic mice harboring a single copy insert of the human protamine cluster were subjected to Micrococcal Nuclease-seq. CENTIPEDE, a hierarchical Bayesian model, was used to identify multiple spatial patterns, "footprints", of MNase-seq reads along the sperm genome. Regions predicted by CENTIPEDE analysis to be bound by a regulatory factor in sperm were correlated with genomic landmarks and higher order chromatin structure datasets to identify potential roles for these factors in regulating either prior or post spermatogenic, i.e., early embryonic events. This approach linked robust endogenous protamine transcription and transgene suppression to its chromatin environment within topologically associated domains. Of the candidate enhancer-bound regulatory proteins, Ctcf, was associated with chromatin domain boundaries in testes and embryonic stem cells. The continuity of Ctcf binding through the murine germline may permit rapid reconstitution of chromatin organization following fertilization. This likely reflects its preparation for early zygotic genome activation and comparatively accelerated preimplantation embryonic development program observed in mouse as compared to human and bull.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
authors.forename: Graham D
authors.initials: GD
authors.lastname: Johnson
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201, USA.|Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Jodar
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201, USA.|Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Pique-Regi
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201, USA.|Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Krawetz
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D002417:Cattle; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D018983:DNA Footprinting / Q000379:methods*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D011479:Protamines / Q000235:genetics*; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D011479:Protamines