Histone locus regulation by the Drosophila dosage compensation adaptor protein CLAMP

Genes Dev. 2017 Jul 15;31(14):1494-1508. doi: 10.1101/gad.300855.117. Epub 2017 Aug 24.

Abstract

The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication-dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA repeat cis elements within the bidirectional histone3-histone4 promoter direct HLB formation in Drosophila In addition, the CLAMP (chromatin-linked adaptor for male-specific lethal [MSL] proteins) zinc finger protein binds these GA repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We demonstrated previously that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X chromosome. Therefore, CLAMP binding to GA repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome.

Keywords: CLAMP; GA repeats; GAGA factor; dosage compensation; histone locus body; nuclear bodies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Chromatin / metabolism
  • Conserved Sequence
  • DNA / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation, Developmental*
  • Genetic Loci*
  • Histones / genetics*
  • Histones / metabolism
  • Promoter Regions, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Transcription Factors / metabolism

Substances

  • CLAMP protein, Drosophila
  • Chromatin
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Histones
  • Transcription Factors
  • Trl protein, Drosophila
  • DNA