?. Grants and . Fellowships, Labex Gral -Individual projects (120k EUR) 2015 -Fondation ARC -Projet Fondation ARC, 2016.

, ATIP/AVENIR start-up grant -CNRS/Plan Cancer (360k EUR+ salary)

, Marie Curie Intra-European postdoctoral fellowship (awarded but declined) 2005 -EMBO long-term postdoctoral fellowship 2001 -Boehringer Ingelheim Fonds PhD scholarship (awarded but declined) 2000 -Fellowship of TEMPRA PECO program of, 2011.

?. Organisation and . Scientific-meetings, Co-organiser of the "Signalling Through Chromatin" international symposium in Grenoble Since 2012 Co-organiser of regular meetings of the Chromatin, 2013.

?. Institutional and . Since, Co-responsible of the Molecular Medicine research axis at the IBS 2009 -2015 Faculty member -EMBL 2009 -2015 Chairing lab committee meetings of the EMBL Grenoble III. Scientific supervision BTS student, 2016.

L. Bastel and -. Paris,

, EMBL) co-author of Dias et al, Genes Dev, vol.28, pp.929-942, 2014.

, EMBL) co-author of Kadlec et al, PhD students: 2012-2015 Jorge Dias -EMBL/University of Heidelberg first author of Dias et al, vol.18, pp.587-600, 2009.

, Since 2016 Shasha Shi (at IBS) 2015-2016 Rong Chen

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, All proteins are from baculovirus-expressed protein extracts. Interacting proteins are indicated by asterisks and highlighted in red. (See Supplemental Fig. S1C for the input sample). (D) Schematic representation of the domain structure of human WDR5 and KANSL1. KANSL1 contains a PEHE domain involved in the binding of MOF (Kadlec et al. 2011) and a WIN motif identified in this study. (E) Ribbon diagram of the minimal human WDR5-KANSL1 complex structure. WDR5 23-334 is shown in yellow, and KANSL1 is in red. The key interacting KANSL1 Arg592 is shown as sticks. (F) Sequence alignment of NSL1 proteins. Only the sequence of the fragment involved in the interaction with WDR5 is shown. Identical residues are in green boxes. Numbering of the motif residues centered on Arg592 (in humans) is shown above the alignment. Representative sequences of corresponding MLL and H3 motifs are aligned with NSL1. (G) Details of the interaction between the b-propeller domain of WDR5 and the WIN motif of KANSL1. Interacting WDR5 residues are shown in orange, and KANSL1 residues are in gray. Residues without side chains represent main chain interactions. Contacts with Arg592 of KANSL1 are similar to the ones of H3 and MLL proteins and are not shown for clarity (see Supplemental Fig. S3B). (H) Interaction interface of the complex between the b-propeller domain of WDS (green) and the WIN motif of NSL1 (red). (I) SDS-PAGE analysis of the binding of His-tagged KANSL1 584-690 (wild type [WT] and the R592A mutant) to coexpressed untagged WDR5 23-334 after purification using Ni 2+ resin. KANSL1 584-690 is only detectable (but still degrading) when bound to WDR5. (J) ITC measurement of the interaction between WDR5 23-334 and the KANSL1 WIN motif-containing peptide (585-DGTCVAARTRPVLS-598-Y). The bottom panel represents a fit of the calorimetric data to single-site-binding model. Dissociation constant (K d ) derived from the fit is indicated. (K) ITC measurement of the interaction between WDR5 23-334 and the mutated KANSL1 WIN motif-containing peptide (585-DGTCVAAATRPVLS-598-Y). (L, toppanel) 3xFlag-WDS was coexpressed with either wild-type NSL1 (WT) or mutant NSL1 (R721A), Figure 1. Structural analysis of the KANSL1-WDR5 interaction. (A) SDS-PAGE and silver staining analysis of Flag pull-down assays using N-terminally 3xFlag-NSL1 as the bait and other untagged NSLs as prey. All proteins are from baculovirus-expressed protein extracts. Interacting proteins are indicated by asterisks and highlighted in red. (See Supplemental Fig. S1A for the input sample). (B) Western blot analysis of the reverse Flag pull-down assays of A using untagged NSL1 as the prey and either N-terminal or C-terminal 3xFlag-tagged NSLs as bait. (FT) Flowthrough sample

, B) complexes. The two complexes were superimposed using WDR5. (C) Flag immunoprecipitation of wild-type (WT) NSL1 and NSL1 R721A in SL-2 cells. Both wild-type nsl1 and nsl1 R721A were transiently transfected into SL-2 cells, and immunoprecipitation was performed using Flag-M2 resin. Antibodies used for Western blot analysis are indicated. (D) Flag immunoprecipitation of wild-type (WT) NSL2 and NSL2 I160E-V162D in stably expressing SL-2 cells. Both wild-type nsl2 and nsl2 I160E-V162D were transfected into SL-2 cells, and stably expressing cells were selected. Immunoprecipitation was performed using Flag-M2 resin. Antibodies used for Western blot analysis are indicated. (E) Western blot analysis of Flag pull-down assays using untagged NSL2 as the prey and either N-terminal or C-terminal 3xFlag-tagged NSLs as bait. (FT) Flowthrough sample. Interacting proteins are highlighted in red. The eluted prey proteins are shown in Supplemental Figure S1D. (F) A schematic representation of the structure of the RE transcript, encoded by nsl1/CG4699, used in this study. Exons (black bars), introns (black lines), and untranslated regions (UTRs) (gray bars) are shown. The ATG start and the STOP codon are indicated as well as the positions of the transposon insertions (black arrows). The site of the introduced mutation disrupting the NSL1 binding to WDS is marked by a white asterisk, Comparison of the crystal structures of human ternary KANSL1-WDR5-KANSL2 (A) and MLL1-WDR5-RbBP5 (Protein Data Bank

, Tb siblings in which endogenous nsl1 is expressed were used as internal controls and scored as 100% viable. The detail of the fly crosses is given in G. The error bars represent standard deviations of three independent crosses. (I) Western blot analysis of proteins extracted from third instar male and female larvae expressing either wild-type or mutant (R721A) NSL1 in the absence of endogenous NSL1. w 1118 larvae were used as a wild-type control. Antibodies used for the Western blot analysis are indicated

, 200 mM NaCl, and 5 mM b-mercaptoethanol. Proteins were eluted with an increasing concentration of imidazole. Samples were analyzed on SDS-PAGE. A His-tagged minimal interacting region of KANSL1 (residues 584-690; wild type or R592A mutant) was coexpressed with untagged WDR5 (residues 23-334) in E. coli BL21Star (DE3, Invitrogen) from pProEXHTb (Invitrogen) and pRSFDuet-1 (Novagen) expression vectors, respectively. Pulldown experiments were performed as above, KANSL1-WDR5 and KANSL2-WDR5 interaction analysis Four constructs of untagged KANSL1 (residues 1-233, 262-537, 537-773, and 777-1105) were each coexpressed with 6xHis-WDR5 (residues 23-334) in E. coli BL21Star (DE3, Invitrogen) from pRSFDuet-1 (Novagen) and pProEXHTb (Invitrogen) expression vectors, respectively. 6xHis-WDR5 was affinity-purified on Ni 2+ chelating Sepharose (GE Healthcare) in 20 mM Tris, p.1

, KANSL2 L411E,V413D (406-YEFSD DEDDVGDG-417), NSL2 wild type, p.155

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