A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling.
Lysine methylation of histones is recognized as an important component of an epigenetic indexing system demarcating transcriptionally active and inactive chromatin domains. Trimethylation of histone H3 lysine 4 (H3K4me3) marks transcription start sites of virtually all active genes. Recently, we reported that the WD40-repeat protein WDR5 is important for global levels of H3K4me3 and control of HOX gene expression. Here we show that a plant homeodomain (PHD) finger of nucleosome remodelling factor (NURF), an ISWI-containing ATP-dependent chromatin-remodelling complex, mediates a direct preferential association with H3K4me3 tails. Depletion of H3K4me3 causes partial release of the NURF subunit, BPTF (bromodomain and PHD finger transcription factor), from chromatin and defective recruitment of the associated ATPase, SNF2L (also known as ISWI and SMARCA1), to the HOXC8 promoter. Loss of BPTF in Xenopus embryos mimics WDR5 loss-of-function phenotypes, and compromises spatial control of Hox gene expression. These results strongly suggest that WDR5 and NURF function in a common biological pathway in vivo, and that NURF-mediated ATP-dependent chromatin remodelling is directly coupled to H3K4 trimethylation to maintain Hox gene expression patterns during development. We also identify a previously unknown function for the PHD finger as a highly specialized methyl-lysine-binding domain.
Wysocka
Joanna
J
Laboratory of Chromatin Biology.
Swigut
Tomek
T
Xiao
Hua
H
Milne
Thomas A
TA
Kwon
So Yeon
SY
Landry
Joe
J
Kauer
Monika
M
Tackett
Alan J
AJ
Chait
Brian T
BT
Badenhorst
Paul
P
Wu
Carl
C
Allis
C David
CD
D000251:Adenosine Triphosphatases / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D034961:Antigens, Nuclear; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014981:Xenopus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
D000251:Adenosine Triphosphatases; D034961:Antigens, Nuclear; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D008239:Lysine; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins