Skip to content
Login Register

#histone variant

3 public questions tagged with this topic.

Regulation of chromatin structure

Which histone variant is enriched at active gene promoters?

H2A variants diversify nucleosome properties through sequence divergence in docking domain and C-terminal tail. H2A.Bbd, also called H2A.B or Barr-body-deficient, is highly divergent, lacking part of acidic patch and bearing shorter C-terminus, resulting in unusually unstable nucleosomes with relaxed DNA wrapping. Genomic profiling shows enrichment across bodies of actively transcribed genes, exclusion from the immediate transcription start site, and anti-correlation with silencing variant macroH2A. Its loose packing facilitates passage of RNA polymerase II, mRNA processing factor recruitment and maintenance of open chromatin at highly expressed tissue-specific loci.

Ref: Chadwick and Willard, NCBI Gene Review, Histone Variant H2A.Bbd Associated with Active Transcription, Mol Cell Biol

View Details
Regulation of chromatin structure

Which histone variant specifically marks DNA double strand breaks?

DNA double strand breaks immediately trigger checkpoint kinases ATM and DNA-PK. Histone variant H2A.X widely replacing small fraction of H2A throughout genome becomes rapidly phosphorylated at serine 139 over domains extending megabases surrounding breaks, forming gamma-H2A.X foci detectable by immunofluorescence. Phosphorylated tail recruits mediator MDC1, ubiquitin ligases RNF8, 53BP1 and BRCA1 complexes promoting nonhomologous end joining and homologous recombination repair pathway choice. CENP-A marks centromere epigenetically, H2A.Z regulates promoter activity, H3.3 deposited at active genes. Gamma-H2A.X serves as sensitive biomarker for damage quantitation used clinically.

Ref: Rogakou et al., J Biol Chem 1998; Alberts et al., Molecular Biology of the Cell, Chapter 5: H2A.X Marks Double Strand Breaks

View Details
Nucleosome Packing

CENP-A is a variant of histone:

Centromeric chromatin contains distinctive histone variant CENP-A that epigenetically specifies centromere location independent of underlying DNA sequence in most eukaryotes. CENP-A resembles canonical histone H3 in histone fold domain sharing about sixty percent similarity, but possesses divergent N-terminus and loop1 centromere targeting domain CATD directing specific deposition via HJURP chaperone during G1. It replaces H3 in subset of nucleosomes at active centromere creating specialized octamer recruiting inner kinetochore. H1 is linker histone, H2A variants include H2A.Z, H4 lacks centromeric-specific variant analogous to CENP-A functionally.

Ref: Palmer et al., 1987 PNAS; Alberts et al., Molecular Biology of the Cell, Chapter 4: CENP-A is Variant of H3

View Details