• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development.

Histone H3 lysine 4 (K4) methylation has been linked to the transcriptional activation in a variety of eukaryotic species. Here we show that a common component of MLL1, MLL2, and hSet1 H3 K4 methyltransferase complexes, the WD40-repeat protein WDR5, directly associates with histone H3 di- and trimethylated at K4 and with H3-K4-dimethylated nucleosomes. WDR5 is required for binding of the methyltransferase complex to the K4-dimethylated H3 tail as well as for global H3 K4 trimethylation and HOX gene activation in human cells. WDR5 is essential for vertebrate development, in that WDR5-depleted X. laevis tadpoles exhibit a variety of developmental defects and abnormal spatial Hox gene expression. Our results are the first demonstration that a WD40-repeat protein acts as a module for recognition of a specific histone modification and suggest a mechanism for reading and writing an epigenetic mark for gene activation.

Pubmed ID: 15960974

Authors

  • Wysocka J
  • Swigut T
  • Milne TA
  • Dou Y
  • Zhang X
  • Burlingame AL
  • Roeder RG
  • Brivanlou AH
  • Allis CD

Journal

Cell

Publication Data

June 17, 2005

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM 53512
  • Agency: NIGMS NIH HHS, Id: R01 GM066977
  • Agency: NCRR NIH HHS, Id: RR001614
  • Agency: NCRR NIH HHS, Id: RR015804

Mesh Terms

  • Animals
  • Cell Line
  • Genes, Homeobox
  • Heterotrimeric GTP-Binding Proteins
  • Histone-Lysine N-Methyltransferase
  • Histones
  • Humans
  • Lysine
  • Macromolecular Substances
  • Methylation
  • Microfilament Proteins
  • Nucleosomes
  • Vertebrates
  • Xenopus laevis