DDM1 Maintains Heterochromatin by Regulating Histone Variants

Abstract

Chromatin remodeling factors efficiently and precisely establish, maintain, regulate, and distinguish between chromatin states in eukaryotes. DECREASE in DNA METHYLATION 1 (DDM1) is an important heterochromatin remodeling factor in plants that is responsible for maintaining heterochromatin DNA methylation and suppressing most transposable elements. Previous studies have predominantly focused on the effects of DDM1 on chromatin, with only a few focusing on its remodeling mechanisms. However, recent studies have greatly advanced understanding of the remodeling functions of DDM1 and, in particular, have clarified the mechanisms involved. In this review, we discuss the newly identified remodeling functions and mechanisms of DDM1. As DDM1 is closely involved in histone variant exchange, we first introduce the main histone variants associated with chromatin states in plants. Next, we focus on how DDM1 promotes the deposition of specific histone variants and describe its other remodeling functions. We propose that the core function of DDM1 is the regulation of histone variant distribution. DDM1 maintains heterochromatin by regulating the deposition of H2A and H3 variants, particularly by facilitating the exchange of specific histone variants.

Keywords: DDM1; TE silencing; chromatin remodeling factors; heterochromatin maintenance; histone variant exchange; histone variants.

Figure 1

The remodeling functions of DDM1 to nucleosomal DNA in heterochromatin. (a) DDM1 remodels and translocates DNA by cyclically hydrolyzing ATP and undergoing conformational changes; (b) DDM1 increases the flexibility of the entry/exit nucleosomal DNA ends, which counters the low DNA accessibility caused by H2A.W. Red arrows indicate the possible directions of DNA translocation; yellow arrows represent the movements of nucleosomal DNA ends.

Figure 2

The remodeling function of DDM1 in depositing specific H2A and H3 variants in Arabidopsis thaliana. (a) In ddm1 mutant plants, H2A.Z and H3.3 are ectopically enriched in heterochromatin, with a moderate increase in H3K27me3, and there may be incorporation of H3K36me3; (b) In wild-type plants, DDM1 evicts H2A.Z and H3.3 and promotes the deposition of H2A.W and H3.1 in heterochromatin, facilitating the enrichment of H3K9me2 and H3K27me1.

Figure 3

The histone variant exchange model of DDM1. DDM1 evicts H2A.Z and unwraps H3.3 nucleosomes and promotes the deposition of H2A.W and H3.1. The function of DDM1 in counteracting the low accessibility of DNA in nucleosomes containing H2A.W may promote the maintenance of H3K9me2 and H3K27me1 subsequently. DDM1 ensures the stability of repressive marks in heterochromatin.