The Regulation and Function of Cohesin and Condensin in Mammalian Oocytes and Spermatocytes

Abstract

Germ cells, such as oocytes and spermatocytes, produce haploid gametes by a special type of cell division called meiosis. The reduction of chromosome number is achieved in meiosis I, in which homologous chromosomes (homologs) are paired and recombined with their counterparts and finally segregated from each other. How meiotic chromosomes behave in a different manner from mitotic chromosomes has been a fascinating problem for cellular and developmental biology. Cohesin and condensin are multi-subunit protein complexes that play central roles in sister chromatid cohesion and chromosome condensation (also segregation), respectively. Recent studies investigating the expression and function of cohesin and condensin in mammalian germ cells greatly advance our understanding of the molecular mechanism underlying the meiotic chromosomal events. Furthermore, accumulating evidence suggests that reduction of cohesin during prophase I arrest in mammalian oocytes is one of the major causes for age-related chromosome segregation error. This review focuses on the regulation and functions of cohesins and condensins during mammalian meiosis.

Micromanipulation of prophase I chromosomes from mouse spermatocytes reveals high stiffness and gel-like chromatin organization

“…The cohesin SMC complex is also present on chromosomes during mitosis, generating sister chromatid cohesion, but it is removed from chromosome arms in mitotic prometaphase, remaining predominately at the centromere 24,25 . In contrast, meiotic prophase I chromosomes contain much less condensin, which does not play a role until later in the meiotic cell division process 5,10,26 . Unlike mitosis, meiotic prophase I chromosomes are organized by cohesin, which participates in sister chromatid cohesion, homologous chromosome pairing, construction of the SC, and crossover formation [9][10][11]26,27 .…”

Micromanipulation of prophase I chromosomes from mouse spermatocytes reveals high stiffness and gel-like chromatin organization

“…Therefore, the function of a large stiffness of meiotic prophase chromosomes is qualitatively consistent with the stress model of CI, which requires a large elastic stiffness to allow a single crossover event to affect a meiotic chromosome along its entire length 18,20 . This higher stiffness, not required or observed for mitotic chromosomes, could originate in the underlying chromatin being more tightly packed and/or crosslinked in meiotic prophase I (e.g., by meiotic cohesin and SC components) 6,9,16,26 . Determining the quantitative dependence of degree of CI and meiotic chromosome stiffness, for example using knockdowns or knockouts of specific proteins involved in CI, could provide tests for the stress-release model.…”

“…First, both meiotic prophase I and mitotic chromosomes show the same underlying structure, i.e. a chromatin gel meshwork crosslinked by protein complexes (possibly predominantly SMC complexes 22,26,30 ). This general model is supported by experiments where both types of chromosome are fully disintegrated when treated with nucleases but maintain their connectivity (remain mechanically connected between pipettes) when treated with proteases, albeit while losing most of their stiffness.…”

“…Future investigations into the SC include the role of synapsis of SYCP1 across meiotic substages and the roles of SYCP2 and SYCP3 2,11,12 . The underlying cohesin core of meiotic chromosomes promises to be an exciting topic for further investigation 6,15,26,27,34 , since when mitotic chromosomes lack condensin, the main mitotic SMC complex, they completely lose their morphology and stiffness 23 . Disruption of the cohesin SMC complex might be expected to drive similar strong effects during meiotic prophase.…”

Meiotic sex chromosome cohesion and autosomal synapsis are supported byEsco2

“…In mitotic cells, this ring-shaped complex is composed of SMC1α, SMC3, RAD21, and one variant of SCC3 (either STAG1/SA1 or STAG2/SA2). In addition to these canonical subunits, meiocytes express several meiosis-specific components: one variant of SMC1α (SMC1β), two variants of RAD21 (RAD21L and REC8), and an additional variant of SCC3 (STAG3/SA3) (reviewed in Nasmyth and Haering (2009), Wood et al (2010), Nasmyth (2011), Haering and Jessberger (2012), Seitan and Merkenschlager (2012), McNicoll et al (2013), Remeseiro and Losada (2013), Rankin (2015), Lee (2017), Ishiguro (2019)).…”