Abstract

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.

Highlights

  • Mammalian genomes are packaged in nucleosomes that wrap DNA around an octamer of two copies each of the four core histones: H2A, H2B, H3, and H4

  • The core histones are each characterized by a histone fold domain that enables them to dimerize in specific antiparallel pairs—H3 with H4, and H2A with H2B—that can further assemble by forming four-helix bundles between dimers, leading to a central H3–H4 tetramer flanked by two H2A–H2B dimers [81]

  • In the simple sponge Amphimedon queenslandica, enhancer long noncoding RNAs are present and associated with chromatin that is marked by an increased ratio of H3K4me1/H3K4me3 compared with promoter long noncoding RNAs, which are associated with chromatin marked by a decreased H3K4me1/H3K4me3 ratio [33]

Read more

Summary

HISTONE MARKS AND METAPHORS

Mammalian genomes are packaged in nucleosomes that wrap DNA around an octamer of two copies each of the four core histones: H2A, H2B, H3, and H4. The language of covalent histone modifications seems to resemble less a histone code [126] than a set of Chinese characters, in which many characters may write the same sound, and reading the characters involves recognizing common elements that are repeated in innumerable different combinations, each with its own meaning for chromatin regulation. Despite this complexity, much progress has been made this century in understanding histone marks, though much remains to be clarified. Phosphorylations that have major roles in regulating transcription and silencing, which are among the best-studied marks, and omit marks with specialized, nontranscriptional roles in DNA repair, recombination, centromere function, and other processes

THE ORIGIN OF MAMMALIAN HISTONE MARKS
HOW DO ACETYLATION MARKS PROMOTE TRANSCRIPTION?
Acetylation of Histone Tails
Disrupting Internucleosomal Contacts
Acetylation Versus Ubiquitylation of H2BK120
Anchoring to Acetylated Promoters
SCAFFOLDS FOR SILENCING
H3K9me3 and H4K20me3
H3K27me3
COTRANSCRIPTIONAL METHYLATIONS
H3K4me
H3K79me
H3K36me
Balancing H3K27 and H3K36 Methylation in Human Health and Disease
PHOSPHORYLATIONS
H3S10ph and H3S28ph
Findings
CONCLUSIONS
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call