The Drosophila MLR COMPASS complex is essential for programming cis-regulatory information and maintaining epigenetic memory during development

Claudia B. Zraly, Abdul Zakkar, John Hertenstein Perez, Jeffrey Ng, Kevin P. White, Matthew Slattery, Andrew K. Dingwall

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The MLR COMPASS complex monomethylates H3K4 that serves to epigenetically mark transcriptional enhancers to drive proper gene expression during animal development. Chromatin enrichment analyses of the Drosophila MLR complex reveals dynamic association with promoters and enhancers in embryos with late stage enrichments biased toward both active and poised enhancers. RNAi depletion of the Cmi (also known as Lpt) subunit that contains the chromatin binding PHD finger domains attenuates enhancer functions, but unexpectedly results in inappropriate enhancer activation during stages when hormone responsive enhancers are poised, revealing critical epigenetic roles involved in both the activation and repression of enhancers depending on developmental context. Cmi is necessary for robust H3K4 monomethylation and H3K27 acetylation that mark active enhancers, but not for the chromatin binding of Trr, the MLR methyltransferase. Our data reveal two likely major regulatory modes of MLR function, contributions to enhancer commissioning in early embryogenesis and bookmarking enhancers to enable rapid transcriptional re-activation at subsequent developmental stages.

Original languageEnglish (US)
Pages (from-to)3476-3495
Number of pages20
JournalNucleic acids research
Issue number7
StatePublished - 2021

Bibliographical note

Funding Information:
National Institutes of Health [R35GM119553 to M.S.]; National Science Foundation [MCB-1413331, MCB-1716431 to A.K.D.]; the modERN Project generated the ChIP-seq data for Cmi, supported by a grant from the National Institutes of Health [U41HG007355 to K.P.W.]; Stocks obtained from the Bloomington Drosophila Stock Center [NIH P40OD018537]. Funding for open access charge: National Science Foundation [MCB 1716431]. Conflict of interest statement. None declared.

Publisher Copyright:
© The Author(s) 2020


  • Animals
  • Cell Line
  • Drosophila Proteins/metabolism
  • Drosophila melanogaster/embryology
  • Ecdysone/pharmacology
  • Enhancer Elements, Genetic
  • Epigenesis, Genetic
  • Gene Expression Regulation, Developmental
  • Histone-Lysine N-Methyltransferase/metabolism
  • Nuclear Receptor Coactivators/metabolism
  • Promoter Regions, Genetic
  • Transcriptional Activation

PubMed: MeSH publication types

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


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