Most histones are assembled into nucleosomes behind the replication fork to package newly synthesized DNA. By contrast, histone variants, which are encoded by separate genes, are typically ...incorporated throughout the cell cycle. Histone variants can profoundly change chromatin properties, which in turn affect DNA replication and repair, transcription, and chromosome packaging and segregation. Recent advances in the study of histone replacement have elucidated the dynamic processes by which particular histone variants become substrates of histone chaperones, ATP-dependent chromatin remodellers and histone-modifying enzymes. Here, we review histone variant dynamics and the effects of replacing DNA synthesis-coupled histones with their replication-independent variants on the chromatin landscape.
Histone variants at a glance Talbert, Paul B; Henikoff, Steven
Journal of cell science,
03/2021, Letnik:
134, Številka:
6
Journal Article
Recenzirano
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Eukaryotic nucleosomes organize chromatin by wrapping 147 bp of DNA around a histone core particle comprising two molecules each of histone H2A, H2B, H3 and H4. The DNA entering and exiting the ...particle may be bound by the linker histone H1. Whereas deposition of bulk histones is confined to S-phase, paralogs of the common histones, known as histone variants, are available to carry out functions throughout the cell cycle and accumulate in post-mitotic cells. Histone variants confer different structural properties on nucleosomes by wrapping more or less DNA or by altering nucleosome stability. They carry out specialized functions in DNA repair, chromosome segregation and regulation of transcription initiation, or perform tissue-specific roles. In this Cell Science at a Glance article and the accompanying poster, we briefly examine new insights into histone origins and discuss variants from each of the histone families, focusing on how structural differences may alter their functions.
What makes a centromere? Talbert, Paul B.; Henikoff, Steven
Experimental cell research,
04/2020, Letnik:
389, Številka:
2
Journal Article
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Centromeres are the eukaryotic chromosomal sites at which the kinetochore forms and attaches to spindle microtubules to orchestrate chromosomal segregation in mitosis and meiosis. Although ...centromeres are essential for cell division, their sequences are not conserved and evolve rapidly. Centromeres vary dramatically in size and organization. Here we categorize their diversity and explore the evolutionary forces shaping them. Nearly all centromeres favor AT-rich DNA that is gene-free and transcribed at a very low level. Repair of frequent centromere-proximal breaks probably contributes to their rapid sequence evolution. Point centromeres are only ~125 bp and are specified by common protein-binding motifs, whereas short regional centromeres are 1–5 kb, typically have unique sequences, and may have pericentromeric repeats adapted to facilitate centromere clustering. Transposon-rich centromeres are often ~100–300 kb and are favored by RNAi machinery that silences transposons, by suppression of meiotic crossovers at centromeres, and by the ability of some transposons to target centromeres. Megabase-length satellite centromeres arise in plants and animals with asymmetric female meiosis that creates centromere competition, and favors satellite monomers one or two nucleosomes in length that position and stabilize centromeric nucleosomes. Holocentromeres encompass the length of a chromosome and may differ dramatically between mitosis and meiosis. We propose a model in which low level transcription of centromeres facilitates the formation of non-B DNA that specifies centromeres and promotes loading of centromeric nucleosomes.
Histones wrap DNA to form nucleosome particles that compact eukaryotic genomes. Variant histones have evolved crucial roles in chromosome segregation, transcriptional regulation, DNA repair, sperm ...packaging and other processes. 'Universal' histone variants emerged early in eukaryotic evolution and were later displaced for bulk packaging roles by the canonical histones (H2A, H2B, H3 and H4), the synthesis of which is coupled to DNA replication. Further specializations of histone variants have evolved in some lineages to perform additional tasks. Differences among histone variants in their stability, DNA wrapping, specialized domains that regulate access to DNA, and post-translational modifications, underlie the diverse functions that histones have acquired in evolution.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Chromosome segregation depends on the attachment of spindle microtubules to sites on chromosomal DNA known as centromeres, through kinetochore protein complexes. Although RNA was found in ...kinetochores in the 1970s, only with recent investigations has evidence emerged that loading of the centromere-specific nucleosomes that form the foundation of the kinetochore may be coupled to centromeric transcription. Centromeric transcripts are bound by several kinetochore proteins that require them for stabilization or localization. At least some centromeres have promoter activity, and many have non-B form DNA that may facilitate their transcription. Whereas other noncoding RNAs regulate gene expression or silence transposons, cotranscriptional assembly of kinetochores is a novel function for noncoding RNAs.
Centromeres are transcribed at a low level and transcripts are incorporated into centromeric chromatin, where they serve essential functions.
Several kinetochore proteins bind centromeric transcripts, which may be necessary to stabilize or localize the proteins.
Loading of centromere-specific nucleosomes may be coupled to centromeric transcription.
Some centromeres have known promoter activity and most centromeres are enriched in non-B form DNA that may facilitate transcription or loading of centromere-specific nucleosomes.
Sophisticated gene-regulatory mechanisms probably evolved in prokaryotes billions of years before the emergence of modern eukaryotes, which inherited the same basic enzymatic machineries. However, ...the epigenomic landscapes of eukaryotes are dominated by nucleosomes, which have acquired roles in genome packaging, mitotic condensation and silencing parasitic genomic elements. Although the molecular mechanisms by which nucleosomes are displaced and modified have been described, just how transcription factors, histone variants and modifications and chromatin regulators act on nucleosomes to regulate transcription is the subject of considerable ongoing study. We explore the extent to which these transcriptional regulatory components function in the context of the evolutionarily ancient role of chromatin as a barrier to processes acting on DNA and how chromatin proteins have diversified to carry out evolutionarily recent functions that accompanied the emergence of differentiation and development in multicellular eukaryotes.
Nucleosomes wrap DNA and impede access for the machinery of transcription. The core histones that constitute nucleosomes are subject to a diversity of posttranslational modifications, or marks, that ...impact the transcription of genes. Their functions have sometimes been difficult to infer because the enzymes that write and read them are complex, multifunctional proteins. Here, we examine the evidence for the functions of marks and argue that the major marks perform a fairly small number of roles in either promoting transcription or preventing it. Acetylations and phosphorylations on the histone core disrupt histone-DNA contacts and or destabilize nucleosomes to promote transcription. Ubiquitylations stimulate methylations that provide a scaffold for either the formation of silencing complexes or resistance to those complexes, and carry a memory of the transcriptional state. Tail phosphorylations deconstruct silencing complexes in particular contexts. We speculate that these fairly simple roles form the basis of transcriptional regulation by histone marks.
Geneticists have long known that centromeres suppress crossing over, but considerable evidence indicates that they appear to recombine. Confirmation of gene conversion in maize centromeres explains ...this paradox.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Centromeres, the chromosomal loci where spindle fibers attach during cell division to segregate chromosomes, are typically found within satellite arrays in plants and animals. Satellite arrays have ...been difficult to analyze because they comprise megabases of tandem head-to-tail highly repeated DNA sequences. Much evidence suggests that centromeres are epigenetically defined by the location of nucleosomes containing the centromere-specific histone H3 variant cenH3, independently of the DNA sequences where they are located; however, the reason that cenH3 nucleosomes are generally found on rapidly evolving satellite arrays has remained unclear. Recently, long-read sequencing technology has clarified the structures of satellite arrays and sparked rethinking of how they evolve, and new experiments and analyses have helped bring both understanding and further speculation about the role these highly repeated sequences play in centromere identification.
Highlights • Histone variants are continually available to respond to environmental stimuli. • Variants employ diverse structures and interactions to modify chromatin. • Histones are widely used ...outside the chromatin in organismal defense. • Study of environmental responses can elucidate epigenetic processes.
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