ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.

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 his...

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Autores principales:	Seth Frietze, Henriette O'Geen, Kimberly R Blahnik, Victor X Jin, Peggy J Farnham
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e228ff23de144c23bd678f87016e3721
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spelling	oai:doaj.org-article:e228ff23de144c23bd678f87016e37212021-11-18T07:01:58ZZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.1932-620310.1371/journal.pone.0015082https://doaj.org/article/e228ff23de144c23bd678f87016e37212010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21170338/?tool=EBIhttps://doaj.org/toc/1932-6203Only 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 3' 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.Seth FrietzeHenriette O'GeenKimberly R BlahnikVictor X JinPeggy J FarnhamPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e15082 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seth Frietze Henriette O'Geen Kimberly R Blahnik Victor X Jin Peggy J Farnham ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.
description	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 3' 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.
format	article
author	Seth Frietze Henriette O'Geen Kimberly R Blahnik Victor X Jin Peggy J Farnham
author_facet	Seth Frietze Henriette O'Geen Kimberly R Blahnik Victor X Jin Peggy J Farnham
author_sort	Seth Frietze
title	ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.
title_short	ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.
title_full	ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.
title_fullStr	ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.
title_full_unstemmed	ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.
title_sort	znf274 recruits the histone methyltransferase setdb1 to the 3' ends of znf genes.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/e228ff23de144c23bd678f87016e3721
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ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.

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