schliessen

Filtern

 

Bibliotheken

Histone demethylase JMJD2B coordinates H3K4/H3K9 methylation and promotes hormonally responsive breast carcinogenesis

It is well-documented that the methylation of histone H3 lysine 4 (H3K4) and of H3K9 are mutually exclusive, an epigenetic phenomenon conserved from yeast to humans. How this opposed methylation modification is accomplished and coordinated in mammalian cells is poorly understood. Here we report that... Full description

Journal Title: Proceedings of the National Academy of Sciences 03 May 2011, Vol.108(18), p.7541
Main Author: Lei Shi
Other Authors: Luyang Sun , Qian Li , Jing Liang , Wenhua Yu , Xia Yi , Xiaohan Yang , Yanyan Li , Xiao Han , Yu Zhang , Chenghao Xuan , Zhi Yao , Yongfeng Shang
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1017374108
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: pnas_s108_18_7541
title: Histone demethylase JMJD2B coordinates H3K4/H3K9 methylation and promotes hormonally responsive breast carcinogenesis
format: Article
creator:
  • Lei Shi
  • Luyang Sun
  • Qian Li
  • Jing Liang
  • Wenhua Yu
  • Xia Yi
  • Xiaohan Yang
  • Yanyan Li
  • Xiao Han
  • Yu Zhang
  • Chenghao Xuan
  • Zhi Yao
  • Yongfeng Shang
subjects:
  • Sciences (General)
ispartof: Proceedings of the National Academy of Sciences, 03 May 2011, Vol.108(18), p.7541
description: It is well-documented that the methylation of histone H3 lysine 4 (H3K4) and of H3K9 are mutually exclusive, an epigenetic phenomenon conserved from yeast to humans. How this opposed methylation modification is accomplished and coordinated in mammalian cells is poorly understood. Here we report that the H3K9 trimethyl demethylase JMJD2B is an integral component of the H3K4-specific methyltransferase, the mixed-lineage leukemia (MLL) 2 complex. We show that the JMJD2B/MLL2 complex is copurified with estrogen receptor α (ERα) and is required for ERα-regulated transcription. We demonstrate that H3K9 demethylation and H3K4 methylation are coordinated in ERα-activated transcription such that H3K9 demethylation is a prerequisite for H3K4 methylation. Significantly, depletion of JMJD2B impairs the estrogen-induced G 1 /S transition of the cell cycle in vitro and inhibits breast tumorigenesis in vivo. Interestingly, JMJD2B itself is an ERα target gene, and forms a feed-forward regulatory loop in regulation of the hormone response. Our results provide a molecular basis for the coordinated H3K4 methylation/H3K9 demethylation in transcription activation, link the trimethyl demethylase JMJD2B to euchromatin functions, and provide a mechanism for JMJD2B in breast carcinogenesis.
language: eng
source:
identifier: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1017374108
fulltext: fulltext_linktorsrc
issn:
  • 0027-8424
  • 00278424
  • 1091-6490
  • 10916490
url: Link


@attributes
ID1049576292
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid108_18_7541
sourceidpnas_s
recordidTN_pnas_s108_18_7541
sourcesystemPC
dbid
0PNE
1RNA
pqid864966255
galeid256456792
display
typearticle
titleHistone demethylase JMJD2B coordinates H3K4/H3K9 methylation and promotes hormonally responsive breast carcinogenesis
creatorLei Shi ; Luyang Sun ; Qian Li ; Jing Liang ; Wenhua Yu ; Xia Yi ; Xiaohan Yang ; Yanyan Li ; Xiao Han ; Yu Zhang ; Chenghao Xuan ; Zhi Yao ; Yongfeng Shang
ispartofProceedings of the National Academy of Sciences, 03 May 2011, Vol.108(18), p.7541
identifier
subjectSciences (General)
descriptionIt is well-documented that the methylation of histone H3 lysine 4 (H3K4) and of H3K9 are mutually exclusive, an epigenetic phenomenon conserved from yeast to humans. How this opposed methylation modification is accomplished and coordinated in mammalian cells is poorly understood. Here we report that the H3K9 trimethyl demethylase JMJD2B is an integral component of the H3K4-specific methyltransferase, the mixed-lineage leukemia (MLL) 2 complex. We show that the JMJD2B/MLL2 complex is copurified with estrogen receptor α (ERα) and is required for ERα-regulated transcription. We demonstrate that H3K9 demethylation and H3K4 methylation are coordinated in ERα-activated transcription such that H3K9 demethylation is a prerequisite for H3K4 methylation. Significantly, depletion of JMJD2B impairs the estrogen-induced G 1 /S transition of the cell cycle in vitro and inhibits breast tumorigenesis in vivo. Interestingly, JMJD2B itself is an ERα target gene, and forms a feed-forward regulatory loop in regulation of the hormone response. Our results provide a molecular basis for the coordinated H3K4 methylation/H3K9 demethylation in transcription activation, link the trimethyl demethylase JMJD2B to euchromatin functions, and provide a mechanism for JMJD2B in breast carcinogenesis.
languageeng
source
version10
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
linktorsrc$$Uhttp://www.pnas.org/content/108/18/7541.abstract$$EView_full_text_in_National_Academy_of_Sciences_(Access_to_full_text_may_be_restricted)
search
creatorcontrib
0Lei Shi
1Luyang Sun
2Qian Li
3Jing Liang
4Wenhua Yu
5Xia Yi
6Xiaohan Yang
7Yanyan Li
8Xiao Han
9Yu Zhang
10Chenghao Xuan
11Zhi Yao
12Yongfeng Shang
titleHistone demethylase JMJD2B coordinates H3K4/H3K9 methylation and promotes hormonally responsive breast carcinogenesis
description

It is well-documented that the methylation of histone H3 lysine 4 (H3K4) and of H3K9 are mutually exclusive, an epigenetic phenomenon conserved from yeast to humans. How this opposed methylation modification is accomplished and coordinated in mammalian cells is poorly understood. Here we report that the H3K9 trimethyl demethylase JMJD2B is an integral component of the H3K4-specific methyltransferase, the mixed-lineage leukemia (MLL) 2 complex. We show that the JMJD2B/MLL2 complex is copurified with estrogen receptor α (ERα) and is required for ERα-regulated transcription. We demonstrate that H3K9 demethylation and H3K4 methylation are coordinated in ERα-activated transcription such that H3K9 demethylation is a prerequisite for H3K4 methylation. Significantly, depletion of JMJD2B impairs the estrogen-induced G 1 /S transition of the cell cycle in vitro and inhibits breast tumorigenesis in vivo. Interestingly, JMJD2B itself is an ERα target gene, and forms a feed-forward regulatory loop in regulation of the hormone response. Our results provide a molecular basis for the coordinated H3K4 methylation/H3K9 demethylation in transcription activation, link the trimethyl demethylase JMJD2B to euchromatin functions, and provide a mechanism for JMJD2B in breast carcinogenesis.

subjectSciences (General)
general
0English
1National Acad Sciences
210.1073/pnas.1017374108
3PNAS (National Academy of Sciences)
4National Academy of Sciences (U.S.)
sourceidpnas_s
recordidpnas_s108_18_7541
issn
00027-8424
100278424
21091-6490
310916490
rsrctypearticle
creationdate2011
addtitleProceedings of the National Academy of Sciences
searchscope
0pnas_full
1pnas4
2pnas5
scope
0pnas_full
1pnas4
2pnas5
lsr45$$EView_full_text_in_National_Academy_of_Sciences_(Access_to_full_text_may_be_restricted)
tmp01
0PNAS (National Academy of Sciences)
1National Academy of Sciences (U.S.)
tmp02
0PNE
1RNA
startdate20110503
enddate20110503
lsr40Proceedings of the National Academy of Sciences, 03 May 2011, Vol.108 (18), p.7541
doi10.1073/pnas.1017374108
citationpf 7541 vol 108 issue 18
lsr30VSR-Enriched:[galeid, pages, pqid]
sort
titleHistone demethylase JMJD2B coordinates H3K4/H3K9 methylation and promotes hormonally responsive breast carcinogenesis
authorLei Shi ; Luyang Sun ; Qian Li ; Jing Liang ; Wenhua Yu ; Xia Yi ; Xiaohan Yang ; Yanyan Li ; Xiao Han ; Yu Zhang ; Chenghao Xuan ; Zhi Yao ; Yongfeng Shang
creationdate20110503
lso0120110503
facets
frbrgroupid7632365307530357850
frbrtype5
newrecords20190724
languageeng
topicSciences (General)
collection
0PNAS (National Academy of Sciences)
1National Academy of Sciences (U.S.)
prefilterarticles
rsrctypearticles
creatorcontrib
0Lei Shi
1Luyang Sun
2Qian Li
3Jing Liang
4Wenhua Yu
5Xia Yi
6Xiaohan Yang
7Yanyan Li
8Xiao Han
9Yu Zhang
10Chenghao Xuan
11Zhi Yao
12Yongfeng Shang
jtitleProceedings of the National Academy of Sciences
creationdate2011
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext_linktorsrc
addata
au
0Lei Shi
1Luyang Sun
2Qian Li
3Jing Liang
4Wenhua Yu
5Xia Yi
6Xiaohan Yang
7Yanyan Li
8Xiao Han
9Yu Zhang
10Chenghao Xuan
11Zhi Yao
12Yongfeng Shang
atitleHistone demethylase JMJD2B coordinates H3K4/H3K9 methylation and promotes hormonally responsive breast carcinogenesis
jtitleProceedings of the National Academy of Sciences
risdate20110503
volume108
issue18
spage7541
issn0027-8424
eissn1091-6490
formatjournal
genrearticle
ristypeJOUR
abstract

It is well-documented that the methylation of histone H3 lysine 4 (H3K4) and of H3K9 are mutually exclusive, an epigenetic phenomenon conserved from yeast to humans. How this opposed methylation modification is accomplished and coordinated in mammalian cells is poorly understood. Here we report that the H3K9 trimethyl demethylase JMJD2B is an integral component of the H3K4-specific methyltransferase, the mixed-lineage leukemia (MLL) 2 complex. We show that the JMJD2B/MLL2 complex is copurified with estrogen receptor α (ERα) and is required for ERα-regulated transcription. We demonstrate that H3K9 demethylation and H3K4 methylation are coordinated in ERα-activated transcription such that H3K9 demethylation is a prerequisite for H3K4 methylation. Significantly, depletion of JMJD2B impairs the estrogen-induced G 1 /S transition of the cell cycle in vitro and inhibits breast tumorigenesis in vivo. Interestingly, JMJD2B itself is an ERα target gene, and forms a feed-forward regulatory loop in regulation of the hormone response. Our results provide a molecular basis for the coordinated H3K4 methylation/H3K9 demethylation in transcription activation, link the trimethyl demethylase JMJD2B to euchromatin functions, and provide a mechanism for JMJD2B in breast carcinogenesis.

pubNational Acad Sciences
doi10.1073/pnas.1017374108
urlhttp://www.pnas.org/content/108/18/7541.abstract
lad01Proceedings of the National Academy of Sciences
pages7541-7546
date2011-05-03