Identification and characterization of the human Set1B histone H3-Lys 4 methyltransferase complex

Jeong Heon Lee, Courtney M. Tate, Jin Sam You, David G. Skalnik

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

We previously identified a mammalian Set1A complex analogous to the yeast Set1/COMPASS histone H3-Lys4 methyltransferase complex (Lee, J.-H., and Skalnik, D. G. (2005) J. Biol. Chem. 280, 41725-41731). Data base analysis indicates that human Set1A protein shares 39% identity with an uncharacterized SET domain protein, KIAA1076, hereafter denoted Set1B. Immunoprecipitation and mass spectrometry reveal that Set1B associates with a ∼450 kDa complex that contains all five noncatalytic components of the Set1A complex, including CFP1, Rbbp5, Ash2, Wdr5, and Wdr82. These data reveal two human protein complexes that differ only in the identity of the catalytic histone methyltransferase. In vitro assays demonstrate that the Set1B complex is a histone methyltransferase that produces trimethylated histone H3 at Lys4. Both Set1A and Set1B are widely expressed. Inducible expression of the carboxyl terminus of either Set1A or Set1B decreases steady-state levels of both endogenous Set1A and Set1B protein, but does not alter the expression of the non-catalytic components of the Set1 complexes. A 123-amino acid fragment upstream of the Set1A SET domain is necessary for interaction with CFP1, Ash2, Rbbp5, and Wdr5. This protein domain is also required to mediate feedback inhibition of Set1A and Set1B expression, which is a consequence of reduced Set1A and Set1B stability when not associated with the methyltransferase complex. Confocal microscopy reveals that Set1A and Set1B each localize to a largely non-overlapping set of euchromatic nuclear speckles, suggesting that Set1A and Set1B each bind to a unique set of target genes and thus make non-redundant contributions to the epigenetic control of chromatin structure and gene expression.

Original languageEnglish (US)
Pages (from-to)13419-13428
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number18
DOIs
StatePublished - May 4 2007
Externally publishedYes

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Forensic Anthropology
Methyltransferases
Histones
Proteins
Immunoprecipitation
Epigenomics
Confocal Microscopy
Chromatin
Mass Spectrometry
Yeasts
Databases
Confocal microscopy
Gene Expression
Amino Acids
Speckle
Gene expression
Yeast
Mass spectrometry
Assays
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Identification and characterization of the human Set1B histone H3-Lys 4 methyltransferase complex. / Lee, Jeong Heon; Tate, Courtney M.; You, Jin Sam; Skalnik, David G.

In: Journal of Biological Chemistry, Vol. 282, No. 18, 04.05.2007, p. 13419-13428.

Research output: Contribution to journalArticle

Lee, Jeong Heon ; Tate, Courtney M. ; You, Jin Sam ; Skalnik, David G. / Identification and characterization of the human Set1B histone H3-Lys 4 methyltransferase complex. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 18. pp. 13419-13428.
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