Histone H3 Lysine 36 Methylation Targets the Isw1b Remodeling Complex to Chromatin

Abstract

bHistone H3 lysine 36 methylation is a ubiquitous hallmark of productive transcription elongation. Despite the prevalence of this histone posttranslational modification, however, the downstream functions triggered by this mark are not well understood. In this study, we showed that H3K36 methylation promoted the chromatin interaction of the Isw1b chromatin-remodeling complex in Saccharomyces cerevisiae. Similar to H3K36 methylation, Isw1b was found at the mid-and 3= regions of transcribed genes genome wide, and its presence at active genes was dependent on H3K36 methylation and the PWWP domain of the Isw1b subunit, Ioc4. Moreover, purified Isw1b preferentially interacted with recombinant nucleosomes that were methylated at lysine 36, and this interaction also required the Ioc4 PWWP domain. While H3K36 methylation has been shown to regulate the binding of numerous factors, this is the first time that it has been shown to facilitate targeting of a chromatin-remodeling complex. Chromatin, a nucleoprotein structure that packages DNA in all eukaryotes, serves as a barrier to numerous nuclear processes, such as transcription, replication, and DNA repair. Numerous mechanisms exist for alteration of chromatin structure, including histone posttranslational modifications, the incorporation of histone variants, and the activity of chromatin-remodeling complexes. There are many examples of these processes functioning in the same pathway, such as histone acetylation, which promotes the binding of the RSC and SWI/SNF remodeling complexes to chromatin (7, 11).Chromatin-remodeling complexes are multisubunit complexes that use the hydrolysis of ATP to disrupt histone-DNA contacts, promoting octamer sliding and histone eviction. Isw1b, a chromatin-remodeling complex found in Saccharomyces cerevisiae, consists of three subunits: Isw1, Ioc2, and Ioc4 (31). This complex localizes to the transcribed regions of genes, where it has been implicated in transcription elongation, termination, and pre-mRNA processing (19). While there have been some insights into how the Isw1b complex functions, how it is targeted to specific regions of the genome is unknown.Transcriptionally active genes are packaged with histones that are mono-, di-, or trimethylated on lysines 4 and 36 of histone H3. Lysine 4 methylation is catalyzed by Set1 as part of the COMPASS complex, which is targeted to transcribed genes through interaction with RNA polymerase II (RNAP II) during the early stages of transcription elongation (26). Lysine 36 methylation is generated by the histone methyltransferase Set2, which similarly interacts with elongating RNAP II, albeit at later stages of elongation. Consistent with the differential interactions of Set1 and Set2 with the various forms of elongating RNAP II, lysine 4 trimethylation (H3K4me3) is predominantly found at the 5= ends of transcribed genes, while lysine 36 di-and trimethylation (H3K36me2 and H3K36me3) are found in the mid-and 3= regions (26).Histone methylation is proposed to act as a docking site for proteins that m...

Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus

“…Transcription elongation NSD1, NSD2 [263] , SET2 [264] , SMYD2 [232] , MMSET [265] ASH1 [266] , JHDM1 [267] , JHDM1A/KDM2A, JHDM1B/KDM2B [268] ISW1B [269] H4K20 me1 me2 me3 (non-genic regions, centromeric heterochromatin, satellite sequences, long terminal repeats Transcritional silencing, heterochromatin, repression of proinflammatory genes PR-SET7/SET8 [270] SUV420H1, SUV420H2 [274] SUV420H2 [274] , SMYD5 [275] PHF8 [271] PHF2 [275] PHF2 [275] L3MBTL1 [272] PHF20 [276] , L3MBTL1 [277] NcoR [275] [ gene [158] . Furthermore, it is well known that a considerable amount of integrated vectors become silent [159] , and this effect seems to be dependent on the promoter chosen to drive the ectopic expression of the gene [160,161] .…”

PWWP domains and their modes of sensing DNA and histone methylated lysines

“…In addition, the PWWP domain of DNMT3a is able to pull down native nucleosomes purified from human cells (Dhayalan et al 2010). Direct nucleosomal binding has been shown to a variety of PWWP-containing proteins, including Pdp1 (Wang et al 2009;Qiu et al 2012), DNMT3a (Dhayalan et al 2010), Ioc4 (Maltby et al 2012;Smolle et al 2012), LEDGF/p75 (Eidahl et al 2013;van Nuland et al 2013), and ZMNYD11 (Guo et al 2014). In all cases, nucleosomal interaction is enhanced by histone methylation.…”

“…5). Mutations of the residues that compose the aromatic cage abolish methylated histone peptide binding (Wang et al 2009Vezzoli et al 2010;Maltby et al 2012;Smolle et al 2012;Wen et al 2014;Gilbert et al 2014;Guo et al 2014). Moreover, this aromatic cage is a common molecular architecture found in members of the Royal superfamily.…”

“…These results first established a functional role for the PWWP domain as a methyl-lysine reader motif involved in epigenetic regulation. After the discovery that Pdp1 PWWP recognizes H4K20me1, many other PWWP domains were shown to exhibit methylated histone-binding activity, including those of BRPF1 (Vezzoli et al 2010;Wu et al 2011), DNMT3a (Dhayalan et al 2010), BRPF2 (Wu et al 2011), HDGF2 (Wu et al 2011), WHSC1 (Wu et al 2011), WHSC1L1 (Wu et al 2011), LEDGF/p75 (Pradeepa et al 2012;Eidahl et al 2013;van Nuland et al 2013), Ioc4 (Maltby et al 2012;Smolle et al 2012), ZMYND11 Wang et al 2014;Guo et al 2014), and Pdp3 (Gilbert et al 2014).…”

Touch, act and go: landing and operating on nucleosomes

“…Deoxynucleotide analogues are used to chemically modify DNA, which thereby becomes site-specifically photoreactive. Moreover, the availability of reconstituted nucleosomes and their semi-synthetic variants bearing specific chemical modifications has enabled the generation of large nucleosome libraries for analytical experiments on binding properties (Montel et al, 2007;Simon, 2010;Maltby et al, 2012;Pichler et al, 2012;Yun et al, 2012;Lee et al, 2013;Rogge et al, 2013;Al-Ani et al, 2014b;David et al, 2015). The EMBO Journal Mechanisms of nucleosome recognition Valentina Speranzini et al the nucleosome is formed by an octamer of tightly associated histone proteins (H2A-H2B) 2 (H3-H4) 2 , and~150 bp of DNA wrapped around the octamer to define a left-handed superhelical fragment (Luger et al, 1997), where the core of the histone proteins is well defined, while the tails mostly lack a defined structure.…”