Less is more: specification of the germline by transcriptional repression

Abstract

In animals, the germline is the only lineage that transmits genetic information to the next generation. Although the founder cells of this lineage are specified differently in invertebrates and vertebrates, recent studies have shown that germline specification in C. elegans, Drosophila and mouse depends on the global inhibition of mRNA transcription. Different strategies are used in each organism, but remarkably most target the same two processes: transcriptional elongation and chromatin remodeling. This convergence suggests that a repressed genome is essential to preserve the unique developmental potential of the germline.

Global transcriptional repression: An initial and essential step for Plasmodium sexual development

“…Global transcriptional repression is generally observed in the initial phase of germ-line formation in metazoan animals (including insects), although the mechanisms of translational repression are variable (13)(14)(15). In mammals, germ-line formation occurs in the early embryo when a small number of PGCs is specified among embryonic cells with a somatic fate (16).…”

A twist of fate: How a meiotic protein is providing new perspectives on germ cell development

“…26,27 Transcriptional quiescence in PGCs is achieved by direct inhibition of RNA polymerase II transcriptional initiation and elongation functions in early embryos by PIE-1 and Pgc in C. elegans and Drosophila, respectively. 3 In C. elegans, loss of pie-1 function leads to mispatterning of embryos and loss of germline lineage. 28,29 In Drosophila, loss of Pgc leads to degeneration of germ cells (pole cells) during midembryogenesis.…”

“…30,31 Transcriptional quiescence in late C. elegans embryos is achieved by controlling chromatin state, specifically inhibition of histone H3K4me2, a mark of active chromatin, and retention of histone H3 lysine 9 methylation (H3K9me), a repressive chromatin mark. 3 Evidence that these marks are important for fecundity came from studies of mutations in spr-5 and met-2 that encode the homologs of the H3K4me2 demethylase LSD1/KDM1 and H3K9me2 methyltransferase SETDB1, respectively. spr-5 and met-2 mutants gradually accumulate H3K4me2 and lose H3K9me over many generations, leading to misexpression of spermatogenesis-enriched genes, reduced brood sizes, and sterility.…”

“…Germ cells are derived from primordial germ cells which are set apart from somatic lineages during early embryogenesis by inheriting specialized cytoplasm called "germ plasm" containing maternally encoded mRNA and proteins. One of the hallmarks of developing PGCs is global transcriptional repression [1][2][3] This repression is thought to be essential to prevent the activation of somatic genes within the germ line.…”

Causes and evolutionary consequences of primordial germ-cell specification mode in metazoans

“…For example, expression of many of the downstream effector genes involved in PGC formation and subsequent germ-line development are often conserved across animals, including nanos, vasa, tudor, and piwi (2). Furthermore, PGCs specified under both modes effectively suppress somatic fate (17,18), presumably to maintain their fate as PGCs. Although the downstream molecular mechanisms underlying PGC fate, expression, and maintenance appear somewhat conserved, it remains unknown why the upstream PGC-specification mechanisms have repeatedly shifted between induction and inheritance among metazoans, and whether these shifts have significant evolutionary consequences.…”