Neurospora importin α is required for normal heterochromatic formation and DNA methylation

PLoS Genetics
Andrew D KlockoEric U Selker

Abstract

Heterochromatin and associated gene silencing processes play roles in development, genome defense, and chromosome function. In many species, constitutive heterochromatin is decorated with histone H3 tri-methylated at lysine 9 (H3K9me3) and cytosine methylation. In Neurospora crassa, a five-protein complex, DCDC, catalyzes H3K9 methylation, which then directs DNA methylation. Here, we identify and characterize a gene important for DCDC function, dim-3 (defective in methylation-3), which encodes the nuclear import chaperone NUP-6 (Importin α). The critical mutation in dim-3 results in a substitution in an ARM repeat of NUP-6 and causes a substantial loss of H3K9me3 and DNA methylation. Surprisingly, nuclear transport of all known proteins involved in histone and DNA methylation, as well as a canonical transport substrate, appear normal in dim-3 strains. Interactions between DCDC members also appear normal, but the nup-6(dim-3) allele causes the DCDC members DIM-5 and DIM-7 to mislocalize from heterochromatin and NUP-6dim-3 itself is mislocalized from the nuclear envelope, at least in conidia. GCN-5, a member of the SAGA histone acetyltransferase complex, also shows altered localization in dim-3, raising the possibility that NUP-6...Continue Reading

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Citations

Jun 12, 2016·Journal of Biochemistry·Yoichi MiyamotoYoshihiro Yoneda
Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jordan D Gessaman, Eric U Selker
Aug 7, 2018·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Masahiro Oka, Yoshihiro Yoneda
Jul 19, 2017·Annual Review of Microbiology·Michael Freitag
Sep 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Shinji HondaEric U Selker
Sep 19, 2020·Nucleic Acids Research·William K StorckEric U Selker
Nov 20, 2016·Proceedings of the National Academy of Sciences of the United States of America·Andrew D KlockoEric U Selker
May 1, 2021·Pathogens·Sara Artigas-JerónimoJosé de la Fuente
Jul 29, 2017·Microbiology Spectrum·Allyson A ErlendsonMichael Freitag
Sep 15, 2021·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kazuya JibikiNoriko Yasuhara

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Datasets Mentioned

BETA
EAA31416.1
U78026.1
GSE61175

Methods Mentioned

BETA
ubiquitination
DamID
immunoprecipitation
ChIP
fluorescence microscopy
co-immunoprecipitation
co-IPs
co-IP
ChIP-seq
Methyl-Seq

Software Mentioned

Integrative Genomics Viewer IGV ) IGVtools
BRAT
Integrative Genomics Viewer
Bowtie
ImageJ
BW
DamID

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