How Human H1 Histone Recognizes DNA

Olesya P. Luzhetskaya, Sergey E. Sedykh, Georgy A. Nevinsky

Research output: Contribution to journalArticlepeer-review

Abstract

Linker H1 histone is one of the five main histone proteins (H1, H2A, H2B, H3, and H4), which are components of chromatin in eukaryotic cells. Here we have analyzed the patterns of DNA recognition by free H1 histone using a stepwise increase of the ligand complexity method; the afinity of H1 histone for various single- and double-stranded oligonucleotides (d(pN)n; n = 1-20) was evaluated using their competition with 12-mer [32P]labeled oligonucleotide and protein-oligonucleotide complex delaying on nitrocellulose membrane filters. It was shown that minimal ligands of H1 histone (like other DNA-dependent proteins and enzymes) are different mononucleotides (dNMPs; Kd = (1.30 ± 0.2) ± 10-2 M). An increase in the length of single-stranded (ss) homo- and hetero-oligonucleotides (d(pA)n, d(pT)n, d(pC)n, and d(pN)n with different bases) by one nucleotide link regardless of their bases, leads to a monotonic increase in their afinity by a factor of f = 3.0 ± 0.2. This factor f corresponds to the Kd value = 1/f characterizing the afinity of one nucleotide of different ss d(pN)n for H1 at n = 2-6 (which are covered by this protein globule) is approximately 0.33 ± 0.02 M. The afinity of five out of six DNA nucleotide units is approximately 25 times lower than for one of the links. The afinity of duplexes of complementary homo- and hetero-d(pN)20 is only 1.3-3.3-fold higher in comparison with corresponding ss oligonucleotides. H1 histone forms mainly weak additive contacts with internucleoside phosphate groups of ssDNAs and one chain of double-stranded DNAs, but not with the bases.

Original languageEnglish
Article number4556
Number of pages15
JournalMolecules
Volume25
Issue number19
DOIs
Publication statusPublished - Oct 2020

Keywords

  • human H1 histone
  • oligonucleotides
  • patterns of DNA recognition
  • LINKER-HISTONE
  • KINETIC BASIS
  • SHORT OLIGONUCLEOTIDES
  • ENZYME INTERACTION
  • I TOPOISOMERASES
  • STRUCTURAL BASIS
  • FPG PROTEIN
  • CHROMATIN
  • REPAIR
  • SUBFRACTIONS
  • Oligonucleotides
  • Human H1 histone
  • Patterns of DNA recognition
  • Humans
  • Oligonucleotides/chemistry
  • DNA, Single-Stranded/chemistry
  • Histones/chemistry

OECD FOS+WOS

  • 3.01 BASIC MEDICAL RESEARCH
  • 1.04 CHEMICAL SCIENCES

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