ZNF274 recruits the histone methyltransferase SETDB1 to the 39 ends of ZNF genes

Seth Frietze, Henriette O'Geen, Kimberly R. Blahnik, Victor X. Jin, Peggy J. Farnham

Research output: Contribution to journalArticle

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Abstract

Only a small percentage of human transcription factors (e.g. those associated with a specific differentiation program) are expressed in a given cell type. Thus, cell fate is mainly determined by cell type-specific silencing of transcription factors that drive different cellular lineages. Several histone modifications have been associated with gene silencing, including H3K27me3 and H3K9me3. We have previously shown that genes for the two largest classes of mammalian transcription factors are marked by distinct histone modifications; homeobox genes are marked by H3K27me3 and zinc finger genes are marked by H3K9me3. Several histone methyltransferases (e.g. G9a and SETDB1) may be involved in mediating the H3K9me3 silencing mark. We have used ChIP-chip and ChIP-seq to demonstrate that SETDB1, but not G9a, is associated with regions of the genome enriched for H3K9me3. One current model is that SETDB1 is recruited to specific genomic locations via interaction with the corepressor TRIM28 (KAP1), which is in turn recruited to the genome via interaction with zinc finger transcription factors that contain a Kruppel-associated box (KRAB) domain. However, specific KRAB-ZNFs that recruit TRIM28 (KAP1) and SETDB1 to the genome have not been identified. We now show that ZNF274 (a KRAB-ZNF that contains 5 C2H2 zinc finger domains), can interact with KAP1 both in vivo and in vitro and, using ChIP-seq, we show that ZNF274 binding sites co-localize with SETDB1, KAP1, and H3K9me3 at the 39 ends of zinc finger genes. Knockdown of ZNF274 with siRNAs reduced the levels of KAP1 and SETDB1 recruitment to the binding sites. These studies provide the first identification of a KRAB domain-containing ZNF that is involved in recruitment of the KAP1 and SETDB1 to specific regions of the human genome.

Original languageEnglish (US)
Article numbere15082
JournalPLoS One
Volume5
Issue number12
DOIs
StatePublished - 2010

Fingerprint

zinc finger motif
methyltransferases
histones
Zinc Fingers
Transcription Factors
Histone Code
transcription factors
Genes
genome
Genome
binding sites
genes
Zinc
Binding Sites
Co-Repressor Proteins
homeotic genes
Homeobox Genes
Gene Silencing
gene silencing
Human Genome

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Frietze, S., O'Geen, H., Blahnik, K. R., Jin, V. X., & Farnham, P. J. (2010). ZNF274 recruits the histone methyltransferase SETDB1 to the 39 ends of ZNF genes. PLoS One, 5(12), [e15082]. https://doi.org/10.1371/journal.pone.0015082

ZNF274 recruits the histone methyltransferase SETDB1 to the 39 ends of ZNF genes. / Frietze, Seth; O'Geen, Henriette; Blahnik, Kimberly R.; Jin, Victor X.; Farnham, Peggy J.

In: PLoS One, Vol. 5, No. 12, e15082, 2010.

Research output: Contribution to journalArticle

Frietze, S, O'Geen, H, Blahnik, KR, Jin, VX & Farnham, PJ 2010, 'ZNF274 recruits the histone methyltransferase SETDB1 to the 39 ends of ZNF genes', PLoS One, vol. 5, no. 12, e15082. https://doi.org/10.1371/journal.pone.0015082
Frietze, Seth ; O'Geen, Henriette ; Blahnik, Kimberly R. ; Jin, Victor X. ; Farnham, Peggy J. / ZNF274 recruits the histone methyltransferase SETDB1 to the 39 ends of ZNF genes. In: PLoS One. 2010 ; Vol. 5, No. 12.
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