Corecognition of DNA and a methylated histone tail by the MSL3 chromodomain

Kim, Dae-Sung; Blus, Bartlomiej J.; Chandra, Vikas; Huang, Peiying; Rastinejad, Fraydoon; Khorasanizadeh, Sepideh

doi:10.1038/nsmb.1856

Cited by 95 publications

(94 citation statements)

References 20 publications

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“…Possible Nucleic Acid Binding Surfaces on the MSL3 CBDIn addition to binding methylated histone tails, we observed that both hMSL3 and dMSL3 chromo-barrel domains bound strongly to nucleic acids when purified from bacterial cell lysates, and remained bound after glutathione-Sepharose affinity purification, an observation consistent with the recent determination of a hMSL3 CBD⅐DNA complex (36). We could only effectively remove contaminating nucleic acid using ionexchange chromatography (results not shown).…”

Section: Effect Of Msl3 Methyllysine Binding Pocket Mutations On Histsupporting

confidence: 68%

“…Comparison with a hMSL3 CBD:DNA H4K20 StructureRecently, a structure of the hMSL3 CBD bound to duplex DNA and H4K20Me 1 was published (36). In contrast to our results, that study concluded that methylated histone tail binding to hMSL3 or dMSL3 CBDs occurred only in the presence of double-stranded DNA and that histone tail binding was significant only for H4K20Me 1 and not other histone tail sequences or higher degrees of methylation.…”

Section: An Aromatic Cage Methyllysine Binding Pocket In Hmsl3-contrasting

confidence: 56%

“…After submission of this manuscript, an independent structural and biochemical study on the Drosophila and human MSL3 CBDs was published (36). The results and conclusions of that study differ in part from those presented in this report and will be discussed in comparison with our findings.…”

contrasting

confidence: 49%

“…However, our hMSL3 atomic model does form dimers, and does contain an extra 3-4 residues visible at the N terminus for four of the five subunits, namely Gly 6 to Phe 9 . Differences at the C terminus of the two independent hMSL3 structure determinations are negligible, as residues 92-101 of the hMSL3⅐DNA complex are not included in the refined model of that structure and hence are likely disordered in solution (36).…”

Section: An Aromatic Cage Methyllysine Binding Pocket In Hmsl3-mentioning

confidence: 99%

“…Although we do not doubt that double-stranded DNA binding to the MSL3 CBD could modulate subsequent in vitro or in vivo methylated histone tail binding, our results suggest that the MSL3 CBD alone is sufficient for in vitro binding to H4K20Me 1 and discrimination over other histone tail sequences. We also note that the other study used dMSL3 and hMSL3 constructs each containing an extra nine N-terminal residues (MKKHHHHHH) to facilitate protein purification and an extra eight residues at the C terminus for hMSL3 ( 94 LRSTGRKK 101 ) (36). The hMSL3 and dMSL3 constructs used in our study contain five extra N-terminal residues (GPLGS) from the cloning vector.…”

Section: An Aromatic Cage Methyllysine Binding Pocket In Hmsl3-mentioning

confidence: 99%

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Structural and Biochemical Studies on the Chromo-barrel Domain of Male Specific Lethal 3 (MSL3) Reveal a Binding Preference for Mono- or Dimethyllysine 20 on Histone H4

Moore

Ferhatoglu

Jia

et al. 2010

Journal of Biological Chemistry

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We have determined the human male specific lethal 3 (hMSL3) chromo-barrel domain structure by x-ray crystallography to a resolution of 2.5 Å (r ‫؍‬ 0.226, R free ‫؍‬ 0.270). hMSL3 contains a canonical methyllysine binding pocket made up of residues Tyr-31, Phe-56, Trp-59, and Trp-63. A six-residue insertion between strands ␤ 1 and ␤ 2 of the hMSL3 chromobarrel domain directs the side chain of Glu-21 into the methyllysine binding pocket where it hydrogen bonds to the NH group of a bound cyclohexylamino ethanesulfonate buffer molecule, likely mimicking interactions with a histone tail dimethyllysine residue. In vitro binding studies revealed that both the human and Drosophila MSL3 chromo-barrel domains bind preferentially to peptides representing the mono or dimethyl isoform of lysine 20 on the histone H4 N-terminal tail (H4K20Me 1 or H4K20Me 2 ). Mutation of Tyr-31 to Ala in the hMSL3 methyllysine-binding cage resulted in weaker in vitro binding to H4K20Me 1 . The same mutation in the msl3 gene compromised male survival in Drosophila. Combined mutation of Glu-21 and Pro-22 to Ala in hMSL3 resulted in slightly weaker in vitro binding to H4K20Me 1 , but the corresponding msl3 mutation had no effect on male survival in Drosophila. We propose MSL3 plays an important role in targeting the male specific lethal complex to chromatin in both humans and flies by binding to H4K20Me 1 . Binding studies on the related dMRG15 chromo-barrel domain revealed that MRG15 prefers binding to H4K20Me 3 . Nuclear histone acetyltransferase (HAT)3 enzymes are found in multiprotein complexes that acetylate specific lysine residues on the N-terminal tails of histone proteins, thereby regulating nucleosome structure, chromatin packaging, and gene expression (1-15). MOF, a conserved member of the MYST (Moz, Ysb2, Sas2, Tip60) family of HAT enzymes, functions as the catalytic subunit in a number of distinct HAT complexes that target gene promoters (8), large contiguous domains of chromatin (3, 4, 14, 15), or non-histone proteins such as p53 (5-7). The precise targeting and substrate specificity of MOF relies on the presence of components distinct from the catalytic subunit (3,4,7,8). Specifically, in the MOFcontaining Drosophila male specific lethal (MSL) complex, the MSL3 protein is required for chromatin targeting, nucleosome binding, histone tail substrate recognition, and maximal MOF HAT activity (16 -20).The most well studied MOF-containing complex is the Drosophila melanogaster male specific lethal or MSL complex that binds selectively to large regions of the X-chromosome in male flies (14,15,(21)(22)(23)(24)(25)(26) where it is enriched at the 3Ј ends of actively transcribed genes (27-30) and acetylates lysine 16 on histone H4 (H4K16Ac) (22, 31), thereby balancing male Xchromosomal gene expression. The Drosophila MSL complex contains the dMSL1, dMSL2, and dMSL3 proteins, the RNA/ DNA helicase MLE, the HAT enzyme MOF, and one of two apparently functionally redundant non-coding RNAs (roX1 and roX2) (reviewed in Refs. 14, 15, and 21). The...

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Section: Effect Of Msl3 Methyllysine Binding Pocket Mutations On Histsupporting

confidence: 68%

Section: An Aromatic Cage Methyllysine Binding Pocket In Hmsl3-contrasting

confidence: 56%

contrasting

confidence: 49%

Section: An Aromatic Cage Methyllysine Binding Pocket In Hmsl3-mentioning

confidence: 99%

Section: An Aromatic Cage Methyllysine Binding Pocket In Hmsl3-mentioning

confidence: 99%

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Structural and Biochemical Studies on the Chromo-barrel Domain of Male Specific Lethal 3 (MSL3) Reveal a Binding Preference for Mono- or Dimethyllysine 20 on Histone H4

Moore

Ferhatoglu

Jia

et al. 2010

Journal of Biological Chemistry

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Structural and histone binding studies of the chromo barrel domain of TIP60

et al. 2018

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Tat-interactive protein 60 consists of an N-terminal chromo barrel domain (TIP60-CB) and a C-terminal acetyltransferase domain and acetylates histone and nonhistone proteins in diverse cellular processes. While TIP60-CB is thought to recognize histone tails, molecular details of this interaction remain unclear. Here, we attempted a quantitative analysis of the interaction between the human TIP60-CB and histone peptides, but did not observe any detectable binding by either fluorescence polarization or isothermal titration calorimetry assays. We also determined the crystal structure of the TIP60-CB alone. Analysis of the apo-structure reveals a putative peptide-binding site that might be occluded by the basic side chain of a residue in a unique β hairpin between the two N-terminal strands of the β barrel, leading to the inability of TIP60-CB to bind histones.

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