The clr1 locus regulates the expression of the cryptic mating-type loci of fission yeast.

Abstract

The mat2-P and mat3-M loci of fission yeast contain respectively the plus (P) and minus (M) mating-type information in a transcriptionally silent state. That information is transposed from the mat2 or mat3 donor locus via recombination into the expressed mating-type locus (mat1) resulting in switching of the cellular mating type. We have identified a gene, named clr1 (for cryptic loci regulator), whose mutations allow expression of the mat2 and mat3 loci. clr1 mutants undergo aberrant haploid meiosis, indicative of transcription of the silent genes. Production of mRNA from mat3 is detectable in clr1 mutants. Furthermore, the ura4 gene inserted near mat3, weakly expressed in wild-type cells, is derepressed in clr1 mutants. The clr1 mutations also permit meiotic recombination in the 15-kb mat2-mat3 interval, where recombination is normally inhibited. The clr1 locus is in the right arm of chromosome II. We suggest that clr1 regulates silencing of the mat2 and mat3 loci, and participates in establishing the "cold spot" for recombination by organizing the chromatin structure of the mating-type region.

SHREC, an Effector Complex for Heterochromatic Transcriptional Silencing

“…SHREC also affects nucleosome positioning at a region downstream of the CAS toward mat2P, consistent with the ubiquitous presence of SHREC and its critical role in maintaining TGS across this region. Mutant cells also displayed noticeable differences in MNase digestion pattern at mat3M, the silencing of which requires SHREC components (Ekwall and Ruusala, 1994;Thon et al, 1994;Thon and Klar, 1992). Despite similar overall changes in nucleosome positioning patterns in both mutants, we noticed that chromatin structure was relatively less perturbed in mit1 K587A cells than in clr3 D232N cells (Figure 6E).…”

“…Mass spectrometry analyses identified the 80 kDa polypeptide as Clr3-FLAG, and the 140 and 65 kDa polypeptides respectively as Clr1, a C2H2-type zinc finger protein, and Clr2, a protein with no obvious conserved domain (Figures 1C and S1) (Bjerling et al, 2004). Clr1, Clr2, and Clr3 were identified in screens for factors required for heterochromatic silencing at the mat locus (Ekwall and Ruusala, 1994;Thon et al, 1994;Thon and Klar, 1992), and previous genetic evidence indicates that Clr1 and Clr3 may function jointly in the same pathway (Grewal et al, 1998). We identified the 90 and 170 kDa bands as Ccq1 and SPBP35G2.10, respectively.…”

Cohesin Impedes Heterochromatin Assembly in Fission Yeast Cells Lacking Pds5

“…In this study, we used a highly sensitive reporter system to perform a systematic screen for factors that affect heterochromatic silencing at the silent mat locus. In addition to identifying previously known heterochromatin assembly factors, such as components of the CLRC (Hong et al 2005;Horn et al 2005;Jia et al 2005), HP1 proteins (Thon and Verhein-Hansen 2000;Sadaie et al 2004), SHREC (Thon and Klar 1992;Ekwall and Ruusala 1994;Thon et al 1994;Sugiyama et al 2007), FACT (facilitates chromatin transcription) (Lejeune et al 2007), andFft3 (Strålfors et al 2011;Taneja et al 2017), we identified eight additional factors. Among the newly identified factors were 60S ribosomal proteins (Rpl2102, Rpl39, and Rpl502) and the 19S proteasome regulatory subunit Rpn10.…”

“…Genetic screens have proven valuable in identifying factors involved in heterochromatin assembly (Thon and Klar 1992;Ekwall and Ruusala 1994;Thon et al 1994;Bayne et al 2014;Zofall et al 2016;Taneja et al 2017;Jahn et al 2018). To uncover additional factors, we used a sensitized reporter system to screen the S. pombe gene deletion library for factors affecting silencing at the silent mat region.…”

“…Spreading requires a unique feature of Clr4 to both "read" and "write" H3K9me (Nakayama et al 2001b;Zhang et al 2008;Al-Sady et al 2013). Clr4-mediated H3K9me deposition also provides binding sites for the chromodomains of HP1 (Heterochromatin Protein 1) family proteins such as Chp2 and Swi6 (Thon and Verhein-Hansen 2000;Bannister et al 2001;Nakayama et al 2001b;Sadaie et al 2004), which in turn create a platform for the recruitment of effectors such as SHREC [Snf2-histone deacetylase (HDAC) repressor complex] containing the Clr1, Clr2, Clr3, and Mit1 proteins (Thon and Klar 1992;Ekwall and Ruusala 1994;Thon et al 1994;Sugiyama et al 2007;Job et al 2016). Interestingly, Swi6 also recruits the cohesin-loading complex that is critical for preferential cohesin enrichment at heterochromatic loci (Bernard et al 2001;Nonaka et al 2002;Fischer et al 2009).…”