Regulation of Swi6/HP1-dependent heterochromatin assembly by cooperation of components of the mitogen-activated protein kinase pathway and a histone deacetylase Clr6.
A study of gene silencing within the mating-type region of fission yeast defines two distinct pathways responsible for the establishment of heterochromatin assembly. One is RNA interference-dependent and acts on centromere-homologous repeats (cenH). The other is a stochastic Swi6 (the fission yeast HP1 homolog)-dependent mechanism that is not fully understood. Here we find that activating transcription factor (Atf1) and Pcr1, the fission yeast bZIP transcription factors homologous to human ATF-2, are crucial for proper histone deacetylation of both H3 and H4. This deacetylation is a prerequisite for subsequent H3 lysine 9 methylation and Swi6-dependent heterochromatin assembly across the rest of the silent mating-type (mat) region lacking the RNA interference-dependent cenH repeat. Moreover, Atf1 and Pcr1 can form complexes with both a histone deacetylase, Clr6, and Swi6, and clr6 mutations affected the H3/H4 acetylation patterns, similar to the atf1 and pcr1 deletion mutant phenotypes at the endogenous mat loci and at the ctt1+ promoter region surrounding ATF/CRE-binding site. These data suggest that Atf1 and Pcr1 participate in an early step essential for heterochromatin assembly at the mat locus and silencing of transcriptional targets of Atf1. Furthermore, a phosphorylation event catalyzed by the conserved mitogen-activated protein kinase pathway is important for regulation of heterochromatin silencing by Atf1 and Pcr1. These findings suggest a role for the mitogen-activated protein kinase pathway and histone deacetylase in Swi6-based heterochromatin assembly.
Kim
Hyun Soo
HS
Research Institute, National Cancer Center, Goyang, Gyeonggi 411-769, Republic of Korea.
Choi
Eun Shik
ES
Shin
Jin A
JA
Jang
Yeun Kyu
YK
Park
Sang Dai
SD
D000123:Acetyltransferases / Q000378:metabolism; D051697:Activating Transcription Factor 1; D051696:Activating Transcription Factors; D018797:Cell Cycle Proteins / Q000737:chemistry*; D002843:Chromatin / Q000737:chemistry; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D017353:Gene Deletion; D020868:Gene Silencing; D005982:Glutathione Transferase / Q000378:metabolism; D006570:Heterochromatin / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D047468:Immunoprecipitation; D008239:Lysine / Q000737:chemistry; D020935:MAP Kinase Signaling System; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D051697:Activating Transcription Factor 1; D051696:Activating Transcription Factors; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C115303:Clr6 protein, S pombe; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D006657:Histones; C097701:Pcr1 protein, S pombe; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C465958:Swi6 protein, S pombe; D014157:Transcription Factors; D000090266:Chromobox Protein Homolog 5; D000123:Acetyltransferases; C116217:ATF2 protein, S cerevisiae; D005982:Glutathione Transferase; D008239:Lysine