ASH1L (a histone methyltransferase protein) is a novel candidate globin gene regulator revealed by genetic study of an English family with beta-thalassaemia unlinked to the beta-globin locus

Br J Haematol. 2016 Nov;175(3):525-530. doi: 10.1111/bjh.14256. Epub 2016 Jul 19.

Abstract

In 1993, we described an English family with beta-thalassaemia that was not linked to the beta-globin locus. Whole genome sequence analyses revealed potential causative mutations in 15 different genes, of which 4 were consistently and uniquely associated with the phenotype in all 7 affected family members, also confirmed by genetic linkage analysis. Of the 4 genes, which are present in a centromeric region of chromosome 1, ASH1L was proposed as causative through functional mRNA knock-down and chromatin-immunoprecipitation studies in human erythroid progenitor cells. Our data suggest a putative role for ASH1L (Trithorax protein) in the regulation of globin genes.

Keywords: ASH1L; Trithorax protein; beta-thalassaemia.

MeSH terms

  • Cell Line
  • Chromosome Mapping
  • DNA-Binding Proteins / metabolism*
  • Erythroid Precursor Cells / cytology
  • Erythroid Precursor Cells / metabolism
  • Gene Expression Regulation*
  • Gene Silencing
  • Genetic Linkage
  • Genetic Variation
  • Genome, Human
  • High-Throughput Nucleotide Sequencing
  • Histone-Lysine N-Methyltransferase
  • Histones / metabolism
  • Humans
  • Phenotype
  • RNA Interference
  • Transcription Factors / metabolism*
  • beta-Globins / genetics*
  • beta-Thalassemia / diagnosis
  • beta-Thalassemia / genetics*
  • beta-Thalassemia / metabolism*

Substances

  • DNA-Binding Proteins
  • Histones
  • Transcription Factors
  • beta-Globins
  • ASH1L protein, human
  • Histone-Lysine N-Methyltransferase