CENP-H-containing complex facilitates centromere deposition of CENP-A in cooperation with FACT and CHD1.
Centromere identity is thought to be determined by epigenetic mechanisms. The centromere-specific histone H3 variant CENP-A plays a central role in specifying the locus where the centromere is constructed. However, the precise mechanisms that target CENP-A to centromeric chromatin are poorly understood. Here, we show that facilitates chromatin transcription (FACT) localizes to centromeres in a CENP-H-containing complex-dependent manner. In conditional mutant cell lines for SSRP1, a subunit of FACT, centromere targeting of newly synthesized CENP-A is severely inhibited. The chromatin remodeling factor CHD1 binds to SSRP1 both in vivo and in vitro and associates with centromeres. The centromeric localization of CHD1 is lost in SSRP1-depleted cells. RNA interference knockdown of CHD1 leads to a decrease in the amount of centromere localized CENP-A. These findings indicate that the CENP-H-containing complex facilitates deposition of newly synthesized CENP-A into centromeric chromatin in cooperation with FACT and CHD1.
Okada
Masahiro
M
*Center for Priority Areas, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan; Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan; Innovative Drug Research Laboratories, Kyowa Hakko Kirin Co., Ltd., Takasaki, Gumma, 370-1295, Japan.
Okawa
Katsuya
K
Isobe
Toshiaki
T
Fukagawa
Tatsuo
T
D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D002645:Chickens; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
D001324:Autoantigens; C000619700:CENPA protein, human; C121933:CENPH protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D046912:Multiprotein Complexes; C073537:SSRP1 protein, human; D035602:Transcriptional Elongation Factors; D004265:DNA Helicases; C080359:CHD1 protein, human