Centromere Dynamics in Male and Female Germ Cells

Abstract

In sexually reproducing organisms the germ line is the cellular lineage that gives rise to gametes. All germ cells originate from germline stem cells that divide asymmetrically to generate gonial pre-cursors, which are amplified in number by mitotic divisions, undergo meiosis and eventually differentiate into mature gametes (haploid eggs and sperm). Information transmitted with gametes is inherited by offspring, and potentially by subsequent generations, instructing in organismal development and beyond. Meiosis comprises one round of DNA replication, followed by two rounds of chromosome segregation; homologous chromosomes segregate in the first division (meiosis I) and sister chromatids segregate in the second division (meiosis II). Important mechanistic features of meiosis occur in substages of prophase I and are critical for genetic recombination, including pairing and synapsis of homologous chromosomes (at leptotene and zygotene), crossing-over (at pachytene), and the appearance of chiasmata (at diplotene/diakinesis). Another unique feature of meiosis is the altered centromere/kinetochore geometry at metaphase I, such that sister kinetochores face the same spindle pole (mono-orientation) and stay together at anaphase I. This chapter reviews centromere dynamics in germ cells, focusing on centromere function and assembly in meiotic cell cycles, as well as centromere inheritance in zygotes. Centromeres are functionally defined by the presence of the histone H3 variant CENP-A, the epigenetic determinant of centromere identity. In most eukaryotes, it is well established that CENP-A function is essential for chromosome segregation in mitosis. CENP-A function in meiosis is less well understood and emerging insights into the differential regulation of meiotic and mitotic CENP-A are discussed.

The Essential Function of SETDB1 in Homologous Chromosome Pairing and Synapsis during Meiosis

“…Meiosis refers to a special type of cell division through which a diploid germ cell undergoes a single round of DNA replication followed by two rounds of divisions to generate haploid gametes. To achieve faithful chromosome segregation during the first meiotic division (meiosis I), homologous chromosomes must form bivalents that interact with the meiotic spindle as a unit in a way that allows homologous centromeres to orient to opposite poles (Dunleavy and Collins, 2017;Gatti et al, 2012;Lane and Kauppi, 2019;Moore and Orr-Weaver, 1998;O'Donnell and O'Bryan, 2014;Radford et al, 2017). Defects in the establishment of homologous bivalents can lead to gametogenic arrest or aneuploidy, resulting in infertility or embryonic loss (Bolcun-Filas and Handel, 2018;Herbert et al, 2015;Jones and Lane, 2012;MacLennan et al, 2015).…”

A dynamic population of prophase CENP-C is required for meiotic chromosome segregation

“…Centromeric CAL1 was observed up to stage 5 oocytes, which could be sufficient to load CID during prophase. The significance of CID prophase loading is not known, but an interesting idea is that it prepares centromeres for meiosis-specific kinetochore functions [ 70 ].…”

Exploring the Potential of Exome Sequencing in Idiopathic Azoospermia: A Genetic Burden and Network Analysis Study

“…Centromere (CEN), CEN complex, and CENP-A nucleosomal complex all take part in centromere organization processes. CENP-A is a histone protein, which is located in centromeric chromatin and replaces histone H3 in mature spermatozoa [80]. In contrast, CENP-C level on spermatids decreases after the second meiotic division in Drosophila [81].…”