Regulatory mechanisms of heterochromatin dynamics during Caenorhabditis elegans meiosis Open Access

Fedotov, Alexander Vyacheslavovich (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/12579s52q?locale=pt-BR%2A
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Abstract

Major changes to higher-order chromatin architecture are tightly linked to all key meiotic processes that ensure proper juxtaposition of homologous chromosomes and their precise segregation during gametogenesis. Heterochromatic domains pose specific challenge for the maintenance of genome stability during homologous recombination due to their repetitive nature. Our understanding of the principles that govern organization of these domains during meiosis is limited. The overall goal of the work described in my dissertation is to determine the mechanisms that regulate dynamics of histone H3 lysine 9 methylation (H3K9me2), a hallmark of heterochromatin, in Caenorhabditis elegans meiosis.

Using a combination of three-dimensional high-resolution microscopy, data mining, and cytogenetic approaches, I revealed previously unrecognized heterochromatin-specific reorganization events at the onset of meiosis that depend upon assembly of meiotic scaffold of chromosomes. I demonstrated that an early association of central region components of synaptonemal complex with chromatin takes place prior to pairing and alignment of homologs, and is mediated by dynein motors. This step of chromosomal axis morphogenesis is required for the establishment of H3K9me2-enriched chromatin compartments, which are later sequestered by the maturing proteinaceous scaffold. I also uncovered the existence of sex-specific differences in the organization of heterochromatin in the context of meiotic scaffold.

My studies therefore provide the first example of the histone modification defining an interface of juxtaposed homologs and point to combinatorial interactions of its regions. They also suggest that chromosomal scaffold itself is an active contributor to compartmentalization of meiotic chromatin, thus potentially playing a role in the prevention of non-allelic recombination, the regulation of genome recognition and defense mechanisms, and the mediation of genome topology.

Table of Contents

Chapter 1: INTRODUCTION

1

Meiosis as a specialized type of cell division

2

Specifics of prophase I events across model organisms

3

C. elegans as a model system for studies of meiosis

6

Spatial organization of prophase I chromatin

8

Chromatin features as factors in regulation of meiotic processes

11

Heterochromatin in meiosis

13

Meiotic sex chromosome inactivation

16

Quality control of meiotic processes

18

RATIONALE

19

SIGNIFICANCE

20

Chapter 2: THE CONSEQUENCES OF THE APPEARANCE OF HETEROCHROMATIC DOMAINS ON UNIVALENTS FOR MEIOTIC PROCESSES

27

Introduction

28

Results

28

Discussion

31

Materials and methods

33

Chapter 3: SYNAPTONEMAL COMPLEX ASSEMBLY LEADS TO COMPARTMENTALIZATION OF HETEROCHROMATIC DOMAINS IN C. ELEGANS MEIOSIS

42

Introduction

43

Results

44

Discussion

67

Materials and methods

75

Chapter 4: SEX-SPECIFIC DIFFERENCES IN HETEROCHROMATIN DYNAMICS IN PROPHASE I OF C. ELEGANS

143

Introduction

144

Results

145

Discussion

147

Materials and methods

150

Chapter 5: SUMMARY AND FUTURE DIRECTIONS

156

REFERENCES

162

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