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PMID:27451393

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Citation

Banday, S, Farooq, Z, Rashid, R, Abdullah, E and Altaf, M (2016) Role of Inner Nuclear Membrane Protein Complex Lem2-Nur1 in Heterochromatic Gene Silencing. J. Biol. Chem. 291:20021-9

Abstract

Heterochromatin in the fission yeast Schizosaccharomyces pombe is clustered at the nuclear periphery and interacts with a number of nuclear membrane proteins. However, the significance and the factors that sequester heterochromatin at the nuclear periphery are not fully known. Here, we report that an inner nuclear membrane protein complex Lem2-Nur1 is essential for heterochromatin-mediated gene silencing. We found that Lem2 is physically associated with another inner nuclear membrane protein, Nur1, and deletion of either lem2 or nur1 causes silencing defect at centromeres, telomeres, and rDNA loci. We analyzed the genome-wide association of Lem2 using ChIP sequencing and we found that it binds to the central core region of centromeres, in striking contrast to Chp1, a component of pericentromeric heterochromatin, which binds H3K9me-rich chromatin in neighboring sequences. The recruitment of Lem2 and Nur1 to silent regions of the genome is dependent on H3K9 methyltransferase, Clr4. Finally, we show that the Lem2-Nur1 complex regulates the local balance between the underln]Snf2/HDAC-containing repressor complex (SHREC) histone deacetylase complex and the anti-silencing protein Epe1. These findings uncover a novel role for Lem2-Nur1 as a key functional link between localization at the nuclear periphery and heterochromatin-mediated gene silencing.

Links

PubMed PMC5025688 Online version:10.1074/jbc.M116.743211

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

SCHPO:MU154

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PomBase:SPAC18G6.10

F

Seeded From UniProt

complete

SCHPO:MU154

is_active_in

GO:0061638: CENP-A containing chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:MU154

involved_in

GO:0070828: heterochromatin organization

ECO:0000269: experimental evidence used in manual assertion

P

Seeded From UniProt

complete

SCHPO:LEM2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PomBase:SPCC4G3.11

F

Seeded From UniProt

complete

SCHPO:LEM2

is_active_in

GO:0061638: CENP-A containing chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:LEM2

is_active_in

GO:0099115: chromosome, subtelomeric region

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:LEM2

is_active_in

GO:0033553: rDNA heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:LEM2

involved_in

GO:0070828: heterochromatin organization

ECO:0000269: experimental evidence used in manual assertion

P

Seeded From UniProt

complete

SCHPO:LEM2

involved_in

GO:0097240: chromosome attachment to the nuclear envelope

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

SCHPO:LEM2

involved_in

GO:0099114: chromatin silencing at subtelomere

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

SCHPO:LEM2

part_of

GO:1902377: nuclear rDNA heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:LEM2

part_of

GO:1904834: nuclear CENP-A containing chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:LEM2

GO:0097355: protein localization to heterochromatin

ECO:0000315:

P

Figure 5A and 5B: S. pombe with loss of heh1 (Lem2; Lap-Emerin-Man domain protein 2) or nur1 show decreased levels of H3K9me2 and Swi6 at the centromere.

complete
CACAO 12389

SCHPO:LEM2

GO:0034506: chromosome, centromeric core domain

ECO:0000314:

C

Organism: S. pombe Protein: Lem2//Lap-Emerin-Man domain protein 2 Due to the interactions with the centromeres in Figure 2, the Lem2 protein is shown to be in the nucleus.

complete
CACAO 12390

SCHPO:LEM2

involved_in

GO:0000183: chromatin silencing at rDNA

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

SCHPO:LEM2

part_of

GO:0005724: nuclear telomeric heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:LEM2

involved_in

GO:0030702: chromatin silencing at centromere

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

SCHPO:MU154

involved_in

GO:0000183: chromatin silencing at rDNA

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

SCHPO:MU154

involved_in

GO:0030702: chromatin silencing at centromere

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

SCHPO:MU154

involved_in

GO:0097240: chromosome attachment to the nuclear envelope

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

SCHPO:MU154

involved_in

GO:0099114: chromatin silencing at subtelomere

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

SCHPO:MU154

part_of

GO:1904834: nuclear CENP-A containing chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SCHPO:MU154

GO:0070868: heterochromatin organization involved in chromatin silencing

ECO:0000316:

UniProtKB:Q10109


P

Organism: Schizosaccharomyces pombe Protein: Nur1//mug154, determined by Val w/ Protein : Lem2//Lap-Emerin-Man domain protein 2 Figure 1C-G: shows the knockout of the complex causes a failure to grow due to a lack of hetreochromatin silencing

complete
CACAO 12545

SCHPO:MU154

GO:0034506: chromosome, centromeric core domain

ECO:0000314:

C

Organism: Schizosaccharomyces pombe Protein: Nur1// mug154 (in paper//in uniprot) Figure 2(F and G): show the localization of Nur1 to the centromere of chromosome 3.

complete
CACAO 12546

SCHPO:MU154

GO:0005724: nuclear telomeric heterochromatin

ECO:0000314:

C

Organism: Schizosaccharomyces pombe Protein: Nur1//mug154 (in paper//in Uniprot) Figure 3: shows the localization of the Nur1 protein to the telomere of chromosome 3.

complete
CACAO 12547

Notes

See also

References

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