title: TALE-light imaging reveals maternally guided, H3K9me2/3-independent emergence of functional heterochromatin in Drosophila embryos.
abstract: Metazoans start embryogenesis with a relatively naïve genome. The transcriptionally inert, late-replicating heterochromatic regions, including the constitutive heterochromatin on repetitive sequences near centromeres and telomeres, need to be re-established during development. To explore the events initiating heterochromatin formation and examine their temporal control, sequence specificity, and immediate regulatory consequence, we established a live imaging approach that enabled visualization of steps in heterochromatin emergence on specific satellite sequences during the mid-blastula transition (MBT) in Drosophila. Unexpectedly, only a subset of satellite sequences, including the 359-base-pair (bp) repeat sequence, recruited HP1a at the MBT. The recruitment of HP1a to the 359-bp repeat was dependent on HP1a's chromoshadow domain but not its chromodomain and was guided by maternally provided signals. HP1a recruitment to the 359-bp repeat was required for its programmed shift to later replication, and ectopic recruitment of HP1a was sufficient to delay replication timing of a different repeat. Our results reveal that emergence of constitutive heterochromatin follows a stereotyped developmental program in which different repetitive sequences use distinct interactions and independent pathways to arrive at a heterochromatic state. This differential emergence of heterochromatin on various repetitive sequences changes their replication order and remodels the DNA replication schedule during embryonic development.
authors.affiliation: Department of Biochemistry, University of California at San Francisco, San Francisco, California 94158, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry, University of California at San Francisco, San Francisco, California 94158, USA.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: O'Farrell
mesh_terms: D000818:Animals; D004261:DNA Replication / Q000235:genetics; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics*; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics*; D006570:Heterochromatin / Q000235:genetics*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D057054:Molecular Imaging; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D006570:Heterochromatin; D006657:Histones
keywords: Drosophila; HP1a; heterochromatin formation; late replication; mid-blastula transition; satellite sequence