Meiotic miRNAs on the X may not escape MSCI after all
Understanding the role of heterochromatin formation to gene regulation has been facilitated by the study of meiotic sex chromosome inactivation (MSCI) in the male germline. The X chromosome becomes incorporated into a heterochromatic structure called the sex body similar to the dosage compensation in mammalian females during development by random inactivation of one of the two X chromosomes and general meiotic silencing that affects the autosomes. MSCI is associated with chromatin positivity for proteins such as gH2AX and BRCA1 and transcriptionally repressive epigenetic modifications like di- and trimethylated H3-K9.
During the pachynema stage of male germ cell prophase most of the X chromosome becomes transcriptionally inactive through chromatin changes; however, prior studies (Song et al. Nat Genet. 2009) had suggested that 86% of the microRNAs (miRNAs) from this chromosome ‑ which account for a substantial fraction of all miRNAs ‑ uniquely escaped this process and are abundant in meiotic and post-meiotic male germ cells. Turner and colleagues provide crucial clarification of this earlier impression. Through the use of RNA fluorescence in situ hybridization (FISH) of the precursor primary miRNAs and mice lacking functional MSCI (e.g., Spo11-/-) or containing an autosomal transgene cluster of X-miRNAs, they demonstrate that MSCI does, in fact, inactivate transcription of male X-miRNAs during pachytene (green in Fig. 1C from the reference below) and that failing to do so results in the death of male germ cells at that stage (aka “pachytene-lethal” mutant class). The authors speculate that the high levels of male X-miRNAs in pachytene spermatocytes previously reported may result from the very long half-life of the mature miRNAs transcribed in spermatogonia rather than from active transcription and processing at that stage of spermatogenesis and the increased spermatocyte cell death caused by a loss of MSCI-based miRNA repression might result from an over reduction of their respective germ cell mRNA targets.
Royo H, Seitz H, ElInati E, Peters AH, Stadler MB, Turner JM. Silencing of X-Linked MicroRNAs by Meiotic Sex Chromosome Inactivation. PLoS Genet. 2015 Oct 28;11(10):e1005461.
Song R, Ro S, Michaels JD, Park C, McCarrey JR, Yan W. Many X-linked microRNAs escape meiotic sex chromosome inactivation. Nat Genet. 2009 Apr; 41(4):488-93. Epub 2009 Mar 22.
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