title: An inverse relationship to germline transcription defines centromeric chromatin in C. elegans.
abstract: Centromeres are chromosomal loci that direct segregation of the genome during cell division. The histone H3 variant CENP-A (also known as CenH3) defines centromeres in monocentric organisms, which confine centromere activity to a discrete chromosomal region, and holocentric organisms, which distribute centromere activity along the chromosome length. Because the highly repetitive DNA found at most centromeres is neither necessary nor sufficient for centromere function, stable inheritance of CENP-A nucleosomal chromatin is postulated to propagate centromere identity epigenetically. Here, we show that in the holocentric nematode Caenorhabditis elegans pre-existing CENP-A nucleosomes are not necessary to guide recruitment of new CENP-A nucleosomes. This is indicated by lack of CENP-A transmission by sperm during fertilization and by removal and subsequent reloading of CENP-A during oogenic meiotic prophase. Genome-wide mapping of CENP-A location in embryos and quantification of CENP-A molecules in nuclei revealed that CENP-A is incorporated at low density in domains that cumulatively encompass half the genome. Embryonic CENP-A domains are established in a pattern inverse to regions that are transcribed in the germline and early embryo, and ectopic transcription of genes in a mutant germline altered the pattern of CENP-A incorporation in embryos. Furthermore, regions transcribed in the germline but not embryos fail to incorporate CENP-A throughout embryogenesis. We propose that germline transcription defines genomic regions that exclude CENP-A incorporation in progeny, and that zygotic transcription during early embryogenesis remodels and reinforces this basal pattern. These findings link centromere identity to transcription and shed light on the evolutionary plasticity of centromeres.
authors.affiliation: Ludwig Institute for Cancer Research and Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, California 92037, USA.
authors.forename: Reto
authors.initials: R
authors.lastname: Gassmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Rechtsteiner
authors.forename: Karen W
authors.initials: KW
authors.lastname: Yuen
authors.forename: Andrew
authors.initials: A
authors.lastname: Muroyama
authors.forename: Thea
authors.initials: T
authors.lastname: Egelhofer
authors.forename: Laura
authors.initials: L
authors.lastname: Gaydos
authors.forename: Francie
authors.initials: F
authors.lastname: Barron
authors.forename: Paul
authors.initials: P
authors.lastname: Maddox
authors.forename: Anthony
authors.initials: A
authors.lastname: Essex
authors.forename: Joost
authors.initials: J
authors.lastname: Monen
authors.forename: Sevinc
authors.initials: S
authors.lastname: Ercan
authors.forename: Jason D
authors.initials: JD
authors.lastname: Lieb
authors.forename: Karen
authors.initials: K
authors.lastname: Oegema
authors.forename: Susan
authors.initials: S
authors.lastname: Strome
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D002503:Centromere / Q000235:genetics*; D000076247:Centromere Protein A; D002843:Chromatin / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D005306:Fertilization; D018507:Gene Expression Regulation, Developmental; D049751:Genome, Helminth; D005854:Germ Cells / Q000378:metabolism*; D006066:Gonads / Q000166:cytology / Q000378:metabolism; D057850:Hermaphroditic Organisms; D008297:Male; D008540:Meiosis; D014158:Transcription, Genetic
chemical_list: D001324:Autoantigens; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone