Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes

Steward, Melissa M.; Lee, Jung Shin; O'Donovan, Aisling; Wyatt, Matt; Bernstein, B; Shilatifard, Ali

doi:10.1038/nsmb1131

Cited by 299 publications

(332 citation statements)

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“…We used siRNA to knock down ASHL2, a core subunit of the SET1/MLL/COMPASS‐like methyltransferase complexes (Shilatifard, 2012), causing efficient reduction in H3K4me3 levels (Fig 7C; see also Steward et al , 2006). We performed FCS for transiently expressed eGFP‐SGF29 in cells previously transfected with siRNA against ASH2L, and observed significantly reduced chromatin interactions (Fig 7D).…”

Section: Resultsmentioning

confidence: 99%

Coactivators and general transcription factors have two distinct dynamic populations dependent on transcription

et al. 2017

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SAGA and ATAC are two distinct chromatin modifying co‐activator complexes with distinct enzymatic activities involved in RNA polymerase II (Pol II) transcription regulation. To investigate the mobility of co‐activator complexes and general transcription factors in live‐cell nuclei, we performed imaging experiments based on photobleaching. SAGA and ATAC, but also two general transcription factors (TFIID and TFIIB), were highly dynamic, exhibiting mainly transient associations with chromatin, contrary to Pol II, which formed more stable chromatin interactions. Fluorescence correlation spectroscopy analyses revealed that the mobile pool of the two co‐activators, as well as that of TFIID and TFIIB, can be subdivided into “fast” (free) and “slow” (chromatin‐interacting) populations. Inhibiting transcription elongation decreased H3K4 trimethylation and reduced the “slow” population of SAGA, ATAC, TFIIB and TFIID. In addition, inhibiting histone H3K4 trimethylation also reduced the “slow” populations of SAGA and ATAC. Thus, our results demonstrate that in the nuclei of live cells the equilibrium between fast and slow population of SAGA or ATAC complexes is regulated by active transcription via changes in the abundance of H3K4me3 on chromatin.

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Section: Resultsmentioning

confidence: 99%

Coactivators and general transcription factors have two distinct dynamic populations dependent on transcription

et al. 2017

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“…Ash2L (Absent, small or homeotic discs-like 2) is a trithorax group protein, and a critical regulator of all MLL complexes. Knockdown of Ash2L results in a global reduction of histone H3K4 trimethylation [3]. The role of Ash2L in methylation regulation is dependent on its two binding partners, RbBP5 and DPY30 [2,4].…”

Section: Dear Editormentioning

confidence: 99%

Structure of the SPRY domain of human Ash2L and its interactions with RbBP5 and DPY30

et al. 2012

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“…In support of a role for human CHD1 in splicing, the depletion of CHD1 from extracts or its RNAi knockdown dramatically reduced splicing efficiency in vitro, and also in pre-mRNA splicing on active genes in vivo. Furthermore, reduction in the level of H3K4 trimethylation using Ash2 RNAi [58] can phenocopy pre-mRNA splicing defects, and results in a reduced association of the U2 snRNP components with chromatin on active genes [57]. Together, this new study suggests that H3K4 trimethlyation could facilitate pre-mRNA maturation via bridging of the spliceosomal components and CHD1 to actively transcribed genes.…”

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Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation

Shilatifard

2008

Current Opinion in Cell Biology

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Chromosomal surfaces are ornamented with a variety of posttranslational modifications of histones, which are required for the regulation of many of the DNA-templated processes. Such histone modifications include acetylation, sumoylation, phosphorylation, ubiquitination and methylation. Histone modifications can either function by disrupting chromosomal contacts or by regulating nonhistone protein interactions with chromatin. In this review, recent findings will be discussed regarding the regulation of the implementation and physiological significance for one such histone modification, histone H3 Lysine 4 (H3K4) methylation by the yeast COMPASS and mammalian COMPASS-like complexes.All DNA-templated processes are regulated by chromatin and its posttranslational modifications. The nucleosome, which is the fundamental unit of chromatin, is composed of 146 base pairs of DNA wrapped twice around an octamer of the four core histones (H3, H4, H2A, and H2B) [1][2][3]. Structural studies demonstrated that the unstructured histone N-terminal tails protrude outward from the nucleosomes and are available for interactions with other neighboring histones or non-histone proteins. Many residues within the histone N-terminal tails and a few within the histone core can be altered by posttranslational modifications [1]. To date, there are at least five types of posttranslational modifications found on histones, these include: acetylation, phosphorylation, ubiquitination, sumoylation, and methylation [4,5]. Almost all of these modifications have been shown to be reversible, and their implementation and removal are fundamental to the regulation of a diverse set of biological processes such as replication, repair, recombination, transcription and RNA processing [4,5]. This review will focus mainly on the most recent studies of one type of histone modification, histone H3 lysine 4 (H3K4) methylation. Histone lysine methylationHistones are methylated either on their arginine and/or lysine residues [6,7]. The lysine residues are methylated on the ε-nitrogen by either the SET domain or the non-SET domain-containing lysine methyltransferases (KMTs). A large number of enzymes have been characterized which are capable of methylating specific lysine residues on histones ( Table 1). The ε-nitrogen can also be modified by lysine acetyl transferases (KATs) and methylation and acetylation of lysine are mutually exclusive. Indeed, many sites of histone methylation are also sites of acetylation.Correspondence and proofs should be sent to the following address: Ali Shilatifard, Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, Office (816) 926-4465, Email: ASH@Stowers-Institute.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable for...

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Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes

Cited by 299 publications

References 12 publications

Coactivators and general transcription factors have two distinct dynamic populations dependent on transcription

Coactivators and general transcription factors have two distinct dynamic populations dependent on transcription

Structure of the SPRY domain of human Ash2L and its interactions with RbBP5 and DPY30

Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation

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