Abstract
Su(var) mutations define epigenetic factors controlling heterochromatin formation and gene silencing in Drosophila. Here, we identify SU(VAR)2-1 as a novel chromatin regulator that directs global histone deacetylation during the transition of cleavage chromatin into somatic blastoderm chromatin in early embryogenesis. SU(VAR)2-1 is heterochromatin-associated in blastoderm nuclei but not in later stages of development. In larval polytene chromosomes, SU(VAR)2-1 is a band-specific protein. SU(VAR)2-1 directs global histone deacetylation by recruiting the histone deacetylase RPD3. In Su(var)2-1 mutants H3K9, H3K27, H4K8 and H4K16 acetylation shows elevated levels genome-wide and heterochromatin displays aberrant histone hyper-acetylation. Whereas H3K9me2- and HP1a-binding appears unaltered, the heterochromatin-specific H3K9me2S10ph composite mark is impaired in heterochromatic chromocenters of larval salivary polytene chromosomes. SU(VAR)2-1 contains an NRF1/EWG domain and a C2HC zinc-finger motif. Our study identifies SU(VAR)2-1 as a dosage-dependent, heterochromatin-initiating SU(VAR) factor, where the SU(VAR)2-1-mediated control of genome-wide histone deacetylation after cleavage and before mid-blastula transition (pre-MBT) is required to enable heterochromatin formation.
Highlights
The stochastic silencing of a gene when juxtaposed to heterochromatic regions by rearrangements or transposition in position-effect variegation (PEV) has been successfully used in Drosophila to reveal epigenetic factors that favor the establishment of either euchromatic or heterochromatic domains (for a review see Girton and Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Johansen 2008; Elgin and Reuter 2013)
Su(var)2-1 belongs to a group of Su(var) genes defined by butyrate/carnitine-sensitive mutations suggesting a function in control of histone deacetylation
Su(var) mutations of gene silencing in position-effect variegation (PEV) in Drosophila have been instrumental in the identification and functional analysis of chromatin components controlling establishment of heterochromatin
Summary
SU(VAR) factors stabilize the repressed chromatin state and are often associated with heterochromatic regions of Drosophila (Elgin and Reuter 2013). Of the estimated 100 Su(var) loci, only about 20% have so far been defined by positional cloning or candidate gene analysis. Amongst those are several prominent factors in the establishment and maintenance of heterochromatin, e.g. the H3K9 methyltransferase (KMTase) SU(VAR) (Tschiersch et al 1994; Rea et al 2000; Schotta et al 2002), the H3K9me2/3-binding protein SU(VAR) (HP1a) (Eissenberg et al 1992; Lachner et al 2001; Fischle et al 2003) and the H3K4 demethylase SU(VAR) (LSD1)
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