Title: Role of chromatin remodelers in regulating the transcriptional switch during meiosis.
Meiosis is a specialized cell division process that produces haploid gametes from a diploid mother cell for sexual reproduction (sperm and egg cells in humans). Chromosome missegregation during meiosis leads to aneuploidy, cancers, birth defects, and miscarriages. The meiotic program is dynamically regulated by stage-specific gene expression and the mechanism of meiosis is conserved from yeast to humans. In budding yeast Saccharomyces cerevisiae, two master transcription factors, Ime1 and Ndt80, control gene expression during meiosis. Ime1 transcribes the early genes (required during S-phase and prophase I), whereas Ndt80 transcribes late genes (required for meiotic chromosome segregation and spore formation from metaphase I to telophase II and spore formation).
Chromatin remodelers (CRs): Eukaryotic DNA is packaged into chromatin with the help of histone proteins (Fig.4A) and this compact DNA is inaccessible for protein binding. CRs are a group of protein complexes that selectively mobilize nucleosomes to create localized areas of nucleosome-depleted chromatin (open chromatin, Fig. 4B) that favors DNA-protein interactions. CRs are well known for their role in transcription activation as they make the gene promoters accessible for transcription factor binding. There are four subfamilies of ATP-dependent CRs in eukaryotes: INO80, CHD/Mi-2, SWI/SNF, ISW1. One of the important, yet unanswered, question in the field is how CRs play a role in regulating the transcriptional switch, a mechanism by which cells switch transcription between the regular transcripts (ORF) and LUTIs
Figure 1. Mechanism of chromatin remodeling and families of chromatin remodelers (CRs).
(A) CRs render DNA accessible for protein binding either by evicting the nucleosomes, sliding the nucleosomes, or exchanging histone variants in the nucleosomes. (B) The four families of ATP-dependent CRs and their complexes. All eight CR complexes have core ATPase subunits, shown in the brackets.
Single Molecule mRNA FISH: Strategy for smFISH probe designing to differentiate between NDC80-LUTI and NDC80-ORF. The Q670 probes (green) hybridize to the common region shared between NDC80-LUTI and NDC80-ORF, whereas the CF590 probes (magenta) hybridize to the unique 5’ region of NDC80LUTI. Representative smFISH images. Scale bar: 5 μm. The relative frequency histograms of cells with a given number of NDC80LUTI and NDC80ORF transcripts per cell, as quantified from smFISH images. ( Chen et al. 2017)