Dynamics of Chromatin Remodeling
11 during Embryonic Development
Gert Jan C. Veenstra
CONTENTS
11.1. Chromatin State: from Packaging DNA to Regulatory Substrate ............................................................................ 173
11.2. Overview of Epigenome Maps: What Is Where, When? ......................................................................................... 174
11.3. Chromatin Accessibility: Opening the Door for Gene Expression .......................................................................... 176
11.3.1. Histone Variants and Linker Histones Modulate Nucleosome Dynamics and Accessibility ............................177
11.3.2. Chromatin Assembly and the Onset of Zygotic Genome Activation ........................................................ 177
11.3.3. Chromatin Accessibility and Transcription Factor Binding ...................................................................... 177
11.4. Histone Modifcations: Acquisition and Dynamics during Early Development ...................................................... 178
11.4.1. Oocyte and Egg Storage Histones and Replication-Coupled Chromatin Assembly Dynamics .......................178
11.4.2. Acquisition of the Antagonistic H3K4me3 and H3K27me3 Marks in the Embryo ................................. 178
11.4.3. Heterochromatin Marks at Repetitive Elements and Near Genes ............................................................. 180
11.5. DNA Methylation: Repression versus Modulation of Histone Modif cations ......................................................... 180
11.5.1. DNA Methylation Dynamics .................................................................................................................... 180
11.5.2. DNA Methylation, Repression and Cross-Talk with Histone Modif cations ............................................ 181
11.6. Future Directions ..................................................................................................................................................... 181
References ............................................................................................................................................................................ 181
11.1. CHROMATIN STATE: FROM PACKAGING
DNA TO REGULATORY SUBSTRATE
Chromatin is the macromolecular complex of genomic DNA
with proteins and RNA, as it is found in the cell nucleus.
The histone proteins account for the majority of the protein
content of chromatin, contributing roughly the same mass as
chromosomal DNA. The basic structural unit of chromatin
is the nucleosome, which consists of an octamer of four histone proteins (histones H2A, H2B, H3, and H4), each present
twice, around which 145–147 base pairs of DNA are wrapped
in a left-handed coil ( Zhou et al. 2019). Both the nucleosomes
and the higher-order folding of nucleosomal DNA contribute
to packaging, condensing, and storing chromosomal DNA
in an orderly fashion. In addition, rather than mere packaging material, chromatin also represents the in vivo substrate
of all processes involving DNA, whether it be transcription,
DNA replication, DNA repair, recombination, mitosis, or
meiosis. The specifc way chromatin is organized at a particular locus therefore holds great regulatory potential at the
molecular level (Perino and Veenstra 2016). First, nucleosome positions matter; gene-regulatory regions tend to have
a nucleosome-free region or exhibit a reduced nucleosome
stability. This is associated with increased accessibility of
the DNA for other molecules, for example, transcription factors (Section 3). Second, the histones are subject to extensive
post-translational modifcations; the modifcations on the
N-terminal tails of histone H3 have been investigated extensively (Bogdanovic et al. 2012; Perino and Veenstra 2016).
Histone modifcations are reversible, involving enzymes with
“writer” and “eraser” activities. Moreover, many of the modifcations are bound by specifc proteins (“readers”), which
bring about the molecular functions of the histone marks.
In Section 4, we will discuss the dynamics of these modifcations. Third, the DNA itself can be reversibly modif ed
both within and between nucleosomes; this occurs predominantly by methylation of cytosine within CpG dinucleotides.
Methylated DNA is bound by methyl-CpG binding proteins.
In addition, methylation status has ramifcations for the
modifcations of the histone tails (Sections 4 and 5). Last,
chromatin is organized in loops and topologically associating domains (TADs), which constitute interaction neighborhoods. Within these neighborhoods, regulatory sequences
such as promoters and enhancers show relatively high interaction frequencies. Many chromatin-associated proteins and
protein complexes play a part in how chromatin and the regulatory sequences and genes it contains are regulated, involving architectural proteins, chromatin remodeling enzymes,
DNA- and chromatin-modifying enzymes, histone chaperones, and DNA-binding proteins and their co-factors.
This chapter will focus on the roles of chromatin in gene
regulation during early embryonic development. We will
highlight insights obtained in Xenopus but will also discuss
the similarities and differences between species where relevant. We will start with an overview of aspects of chromatin
that have been studied in Xenopus tropicalis and Xenopus
laevis, including epigenome maps that represent a valuable
community resource (Section 2). This will be followed by
DOI: 10.1201/9781003050230-13
173
11 during Embryonic Development
Gert Jan C. Veenstra
CONTENTS
11.1. Chromatin State: from Packaging DNA to Regulatory Substrate ............................................................................ 173
11.2. Overview of Epigenome Maps: What Is Where, When? ......................................................................................... 174
11.3. Chromatin Accessibility: Opening the Door for Gene Expression .......................................................................... 176
11.3.1. Histone Variants and Linker Histones Modulate Nucleosome Dynamics and Accessibility ............................177
11.3.2. Chromatin Assembly and the Onset of Zygotic Genome Activation ........................................................ 177
11.3.3. Chromatin Accessibility and Transcription Factor Binding ...................................................................... 177
11.4. Histone Modifcations: Acquisition and Dynamics during Early Development ...................................................... 178
11.4.1. Oocyte and Egg Storage Histones and Replication-Coupled Chromatin Assembly Dynamics .......................178
11.4.2. Acquisition of the Antagonistic H3K4me3 and H3K27me3 Marks in the Embryo ................................. 178
11.4.3. Heterochromatin Marks at Repetitive Elements and Near Genes ............................................................. 180
11.5. DNA Methylation: Repression versus Modulation of Histone Modif cations ......................................................... 180
11.5.1. DNA Methylation Dynamics .................................................................................................................... 180
11.5.2. DNA Methylation, Repression and Cross-Talk with Histone Modif cations ............................................ 181
11.6. Future Directions ..................................................................................................................................................... 181
References ............................................................................................................................................................................ 181
11.1. CHROMATIN STATE: FROM PACKAGING
DNA TO REGULATORY SUBSTRATE
Chromatin is the macromolecular complex of genomic DNA
with proteins and RNA, as it is found in the cell nucleus.
The histone proteins account for the majority of the protein
content of chromatin, contributing roughly the same mass as
chromosomal DNA. The basic structural unit of chromatin
is the nucleosome, which consists of an octamer of four histone proteins (histones H2A, H2B, H3, and H4), each present
twice, around which 145–147 base pairs of DNA are wrapped
in a left-handed coil ( Zhou et al. 2019). Both the nucleosomes
and the higher-order folding of nucleosomal DNA contribute
to packaging, condensing, and storing chromosomal DNA
in an orderly fashion. In addition, rather than mere packaging material, chromatin also represents the in vivo substrate
of all processes involving DNA, whether it be transcription,
DNA replication, DNA repair, recombination, mitosis, or
meiosis. The specifc way chromatin is organized at a particular locus therefore holds great regulatory potential at the
molecular level (Perino and Veenstra 2016). First, nucleosome positions matter; gene-regulatory regions tend to have
a nucleosome-free region or exhibit a reduced nucleosome
stability. This is associated with increased accessibility of
the DNA for other molecules, for example, transcription factors (Section 3). Second, the histones are subject to extensive
post-translational modifcations; the modifcations on the
N-terminal tails of histone H3 have been investigated extensively (Bogdanovic et al. 2012; Perino and Veenstra 2016).
Histone modifcations are reversible, involving enzymes with
“writer” and “eraser” activities. Moreover, many of the modifcations are bound by specifc proteins (“readers”), which
bring about the molecular functions of the histone marks.
In Section 4, we will discuss the dynamics of these modifcations. Third, the DNA itself can be reversibly modif ed
both within and between nucleosomes; this occurs predominantly by methylation of cytosine within CpG dinucleotides.
Methylated DNA is bound by methyl-CpG binding proteins.
In addition, methylation status has ramifcations for the
modifcations of the histone tails (Sections 4 and 5). Last,
chromatin is organized in loops and topologically associating domains (TADs), which constitute interaction neighborhoods. Within these neighborhoods, regulatory sequences
such as promoters and enhancers show relatively high interaction frequencies. Many chromatin-associated proteins and
protein complexes play a part in how chromatin and the regulatory sequences and genes it contains are regulated, involving architectural proteins, chromatin remodeling enzymes,
DNA- and chromatin-modifying enzymes, histone chaperones, and DNA-binding proteins and their co-factors.
This chapter will focus on the roles of chromatin in gene
regulation during early embryonic development. We will
highlight insights obtained in Xenopus but will also discuss
the similarities and differences between species where relevant. We will start with an overview of aspects of chromatin
that have been studied in Xenopus tropicalis and Xenopus
laevis, including epigenome maps that represent a valuable
community resource (Section 2). This will be followed by
DOI: 10.1201/9781003050230-13
173