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 length1–3. 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 epigenetically propagate centromere identity4. 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.

Maize centromeres expand and adopt a uniform size in the genetic background of oat

“…Thus, CENH3 chromatin is probably far less compatible with regulated transcription. In addition, gene transcription may actively evict CENH3 nucleosomes during periods of development when they cannot be readily replaced (Gassmann et al 2012). Our data strongly support this extensive literature by demonstrating that 12 transcribed genes found in nCenM3 and nCen3 were all located within subdomains depleted of CENH3.…”

Cell Biology of theCaenorhabditis elegansNucleus

“…These centromeres are discrete point centromeres distributed throughout the chromosomes, each containing a single nucleosome with the centromere-specific histone H3 variant, HCP-3 (a CENP-A homolog, also known as CenH3) (Steiner and Henikoff 2014). Furthermore, C. elegans centromeres tend to associate with regions of low transcriptional activity, possibly due to exclusion of HCP-3 by high histone turnover in regions with active transcription (Gassmann et al 2012;Steiner and Henikoff 2014). Second, the distribution of active genes along C. elegans autosomes is nonrandom, such that the density of active genes is higher in the center than along the arms (Figure 3).…”

Plasticity and Epigenetic Inheritance of Centromere-specific Histone H3 (CENP-A)-containing Nucleosome Positioning in the Fission Yeast

“…In our assay, we also tested the effect of Cnp1 overexpression and consistently found that nearly all cells carrying the centromeric ade6 ϩ marker form red colonies under conditions of Cnp1 overexpression. Correlation between CENP-A occupancy and gene silencing is also reported in Candida albicans neocentromeres, the newly formed functional centromeres at ectopic sites upon loss of the endogenous centromere (52), and in C. elegans, in which CENP-A is distributed broadly throughout the whole chromatin but inversely correlating with transcription of the underlying chromatin regions in germ line (2). Also, reduction or increase in the Cnp1/histone H3 ratio led to reduced or enhanced gene silencing, respectively, in centromere (37).…”

“…On the other hand, studies in C. elegans embryos showed that in cell divisions, parental CeCENP-A molecules undergo complete turnover after replication. A spatial cue for new CeCENP-A incorporation, instead, is provided by the transcription activity in the germ line (2). Thus, the CENP-A nucleosome inheritance process is unlikely to be conserved in this organism with holocentromeres.…”

“…Noticeable exceptions include the nematode Caenorhabditis elegans, in which the microtubule binding sites are distributed throughout the chromosome instead of being restricted at a discrete single locus (2), and several closely related fungal species represented by Saccharomyces cerevisiae, in which a specific 125-bp DNA segment is sufficient to direct centromere and kinetochore assembly (3,4). In most cases, epigenetic markers (in particular, nucleosomes containing a unique histone H3 variant, CENP-A (or CenH3)) play a pivotal role in determining the location of centromere on each chromosome.…”