Trends in Cell Biology
ReviewHistone Variants and Histone Modifications in Neurogenesis
Section snippets
Histone Variants and Histone Modifications Are Critical for the Dynamic Modulation of Neurogenesis
In eukaryotes, nucleosomes form the basic repeating units of chromatin and comprise core histones (H2A, H2B, H3, and H4). The nucleosomes provide functional complexity via the incorporation of histone variants, which in turn regulate chromatin architecture and gene expression. Histone variants contribute to extending the information potential of the genetic code. They also regulate normal brain function, and other forms of histone modifications have been linked to neurogenesis and neural
Histone Variants in Neurogenesis
Histone variants are structural components of chromatin; they are deposited onto chromatin by specific histone chaperones and interact with other chromatin modifiers (Table 1) [7,8]. Replacing canonical histones with histone variants affects the stability of nucleosomes and contributes to the production of functional chromatin domains [9]. Here, we mainly focus on variants of the H2A family and H3 family, which participate in the regulation of development (Figure 1).
The histone H2A family has
Histone Modifications in Neurogenesis
While histone variants affect neurogenesis, histone modifications, such as histone methylation, acetylation, phosphorylation, ubiquitination, crotonylation, and glycosylation, also directly or indirectly affect neurodevelopmental processes through different mechanisms. Abnormal histone modifications cause a series of neurological diseases and seriously endanger human health. Common histone modifications include methylation, acetylation, phosphorylation, and ubiquitination. Lysine (Lys or K) and
Interactions between Histone Modification and other Epigenetic Modifications
In the earlier sections, we described the different types of histone variant and histone modification in neurodevelopment. In terms of regulatory functions, these epigenetic mechanisms are seldom isolated but interact. We take H3K36me3, an important histone modification described earlier, as an example.
In the section on histone variants, we mentioned that H2A.Z regulates the differentiation of NPCs into neurons by targeting the Nkx2-4 promoter through interaction with H3K36me3
Dynamic Regulation of the 3D Genome in Neurogenesis
Genome architecture has a key role in gene transcription regulation and neural development. As sequencing-based technologies have developed, 3D genome studies have revealed high-order chromatin structures, including A/B compartments, topologically associated domains (TADs), and chromatin loops (Box 1) [6]. What is the role of 3D genomic organization in neural development? Chromatin dynamic changes are crucial in cell fate commitment. Recent studies showed chromatin global compaction during
Histone Dysregulation in Neurological Disorders
Mutations in histone variants are associated with various neurological disorders. For example, mutations in macroH2A have been identified as causing intellectual disability syndrome and Liebenberg syndrome, which is characterized by microcephaly and limb malformations [69]. In addition, mutations in H2BC13 and H2BC21 are associated with intellectual disability, which causes delayed development and intellectual disability [70]. Genetic variations of histone variant H4-16 are associated with
Concluding Remarks and Future Perspectives
Recently, epigenetic factors were found to be increasingly involved in modulating neurogenesis and the pathogenesis of neurodevelopmental disorders. There is now an urgent need to reveal how histone variants and modifications, two main parts of epigenetic factors, affect neurogenesis.
Among the various histone variants, H2A.Z and H3.3 are closely related to neurogenesis. H2A.Z and H3.3 separately recruit histone-modifying enzymes to regulate the transcriptional activity of downstream
Acknowledgments
This work was supported by grants from the CAS Strategic Priority Research Program (XDA16020602), the National Key R&D Program of China (2019YFA0110300), the National Natural Science Foundation of China (81825006, 31730033 and 31621004), and K.C. Wong Education Foundation.
Glossary
- Antisilencing function 1 a (ASF1a)
- gene encoding a member of the H3/H4 family of histone chaperone proteins; is similar to the antisilencing function-1 gene in yeast. The protein is a key component of a histone donor complex that functions in nucleosome assembly. It interacts with histones H3 and H4 and functions together with a chromatin assembly factor during DNA replication and repair.
- Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq)
- useful method to map
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These authors contributed equally to this work