DICER regulates the expression of major satellite repeat transcripts and meiotic chromosome segregation during spermatogenesis

Abstract

Constitutive heterochromatin at the pericentric regions of chromosomes undergoes dynamic changes in its epigenetic and spatial organization during spermatogenesis. Accurate control of pericentric heterochromatin is required for meiotic cell divisions and production of fertile and epigenetically intact spermatozoa. In this study, we demonstrate that pericentric heterochromatin is expressed during mouse spermatogenesis to produce major satellite repeat (MSR) transcripts. We show that the endonuclease DICER localizes to the pericentric heterochromatin in the testis. Furthermore, DICER forms complexes with MSR transcripts, and their processing into small RNAs is compromised in Dicer1 knockout mice leading to an elevated level of MSR transcripts in meiotic cells. We also show that defective MSR forward transcript processing in Dicer1 cKO germ cells is accompanied with reduced recruitment of SUV39H2 and H3K9me3 to the pericentric heterochromatin and meiotic chromosome missegregation. Altogether, our results indicate that the physiological role of DICER in maintenance of male fertility extends to the regulation of pericentric heterochromatin through direct targeting of MSR transcripts.

Roles of piRNAs in transposon and pseudogene regulation of germline mRNAs and lncRNAs

“…Dicer facilitates the degradation of MIWI cleavage products and other double-strand satellite RNAs. These findings, supported by another latest study on Dicer [ 128 ], start to reveal a direct role of PIWI proteins and satellite RNAs in chromosome segregation during meiosis.…”

Sequence, Chromatin and Evolution of Satellite DNA

“…Interference with MaSat transcripts using locked nucleic acid (LNA)-DNA gapmers results in developmental arrest before completion of chromocenter formation [ 231 ]. Mouse pericentric satellites are also expressed during spermatogenesis to produce MaSat repeat transcripts that are involved in the recruitment of SUV39H2, which trimethylates H3K9 on the pericentric heterochromatin required for meiotic chromosome segregation [ 232 ]. Additionally, transcription from MaSats increases significantly during neuronal differentiation, implying that satellite transcripts might play a role in differentiating post-mitotic neurons [ 233 ].…”

IGSF11 is required for pericentric heterochromatin dissociation during meiotic diplotene

“…Within mouse spermatocytes, PCH undergoes dynamic assembly and dissociation during meiotic prophase I, and more importantly, the dynamics of PCH is highly correlated with that of the SC (Figs 6A and S7A, and [38,39]), suggesting that the dynamics of PCH is also regulated and coordinated by the meiotic program. A few proteins have been reported to be involved in the regulation of PCH in mouse spermatocytes, including SUV39H1/SUV39H2 [40], YY1 [41], H1Pγ [42], and DICER [43], but the functions of none of these proteins is restricted only to the PCH region. It is therefore important to note that the phenotypes observed in these mutants may also be the result of a deficiency of protein functions in other chromosomal or cellular regions.…”