Epigenetic maintenance of the expression state of the genome is critical for development. Drosophila GAGA factor interacts with FACT and modulates chromatin structure for the maintenance of gene expression. Here we show that the GAGA factor-FACT complex and its binding site just downstream from the white gene are crucial for position effect variegation. Interestingly there is a dip of histone H3 Lys 9 methylation and a peak of H3 Lys 4 methylation at this site. The GAGA factor and FACT direct replacement of histone H3 by H3.3 through association of HIRA at this site, and maintain white expression under the heterochromatin environment. Based on these findings we propose that the GAGA factor and FACT-dependent replacement of Lys 9-methylated histone H3 by H3.3 counteracts the spreading of silent chromatin.[Keywords: GAGA factor; FACT; histone H3.3; position effect variegation; heterochromatin] Supplemental material is available at http://www.genesdev.org.
Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian nucleosome acetyltransferase of H4 (NuA4) complexes, are coexpressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development. Taking these observations together, we reveal an essential role of the NuA4 complexes for histone hyperacetylation and subsequent compaction of the spermatid genome.KEYWORDS EPC1, TIP60, histone acetylation, spermiogenesis, spermatids, mouse G ametogenesis is a critical step for transmitting both genetic and epigenetic information to the next generation and is regulated in an asymmetric manner between males and females. In mammals, this asymmetry is partly represented by mechanisms to convey the respective haploid genomes by using either nucleoprotamines or nucleosomes. Indeed, most of the sperm genome is intensively compacted by protamines (PRMs) while in oocytes the genome retains nucleosomes. Global replacement of histones by PRMs occurring only in male germ cells during spermiogenesis (the postmeiotic phase of spermatogenesis) plays a role in establishing such asymmetry.During spermiogenesis, male germ cells undergo sequential changes in cell morphology and condensation of the nucleus as represented by the stepwise emergence of round, elongating, condensing, and condensed spermatids (1). Spermatid development in mice is arbitrarily divided into 16 steps based on cell shapes and structures of the nuclei and acrosome, as schematically summarized in Fig. 1A. Spermatids of steps 1 to 8, which are also designated round spermatids (RSs), possess sphere-shaped cells and nuclei. The acrosome is recognized as early as step 3 as a vesicle and develops to form a cap-like structure covering a prospective apical hemisphere of the nucleus by step 8. Elongating spermatids (ESs) of steps 9 to 11 exhibit elongation of the nucleus and concomitant extension of the acrosome along the dorsal surface of the nucleus. Replacement of histones by transition proteins (TNPs) and subsequently by PRMs occurs in condensing spermatids of steps 12 to 14. In steps 15 and 16 condensed spermatids (spermatozoa) exhibit a typical hook type head morphology and are ready to be released into the lumen of seminiferous tubules. In the RSs of steps 1 to 8,
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.