NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE185921 Query DataSets for GSE185921
Status Public on Dec 08, 2022
Title Clustered PHD domains in KMT2/MLL proteins are attracted by H3K4me3 and H3 acetylation-rich active promoters and enhancers
Organism Homo sapiens
Experiment type Other
Summary Histone lysine-specfic methyltransferase 2 (KMT2A-D) proteins, alternatively called mixed lineage leukaemia (MLL1-4) proteins, mediate positive transcriptional memory. As the catalytic subunits of human COMPASS-like complexes, they methylate H3K4 at promoters and enhancers. KMT2A-D contain understudied highly conserved triplets and a quartet of plant homeodomains (PHDs). Here, we show that all clustered PHDs localise to the well-defined loci of H3K4me3 and H3 acetylation-rich active promoters and enhancers. Surprisingly, we observe little difference in binding pattern between PHDs from promoter-specific KMT2A-B and enhancer-specific KMT2C-D. Fusion of the KMT2A CXXC domain to the PHDs drastically enhances their preference for promoters over enhancers. Hence, the presence of CXXC domains in KMT2A-B, but not KMT2C-D, may explain the promoter/enhancer preferences of the full-length proteins. Importantly, targets of PHDs overlap with KMT2A targets and are enriched in genes involved in the cancer pathways. We also observe that PHDs of KMT2A-D are mutated in cancer, especially within conserved folding motifs (Cys4HisCys2Cys/His), which cause a domain loss-of-function. Taken together, our data suggests that PHDs of KMT2A-D guide the full-length proteins to active promoters and enhancers, and thus play a role in positive transcriptional memory.
 
Overall design GreenCUT&RUN experiment in 2 replicates of six different stable HeLa cell lines, expresing NLS-EYFP-tagged clustered PHD domains. Control sample for MACS2 peak calling was HeLa cells from correspoding experiment. In addition, 2 replicates of CUT&RUN in HeLa S3 cells with antibodies against three COMPASS complex subunits and eleven various histone marks. Control sample for MACS2 peak calling was IgG from corresponding experiment.

Please note that each merged processed data was generated from both replicates and is linked to the corresponding rep1 sample records -or- as Series supplementary files
Web link https://link.springer.com/article/10.1007/s00018-022-04651-1
 
Contributor(s) Stroynowska-Czerwińska AM, Bochtler M
Citation(s) 36598580
Submission date Oct 14, 2021
Last update date Jan 13, 2023
Contact name Anna Maria Stroynowska-Czerwińska
E-mail(s) asczerwinska@iimcb.gov.pl
Organization name International Institute of Molecular and Cell Biology
Department Laboratory of Structural Biology
Street address Trojdena 4
City Warszawa
ZIP/Postal code 02-109
Country Poland
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (58)
GSM5627234 HeLa_rep1
GSM5627235 HeLa_rep2
GSM5627236 NLS-EYFP_rep1
Relations
BioProject PRJNA771366
SRA SRP341424

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE185921_IgG12_merged.bigwig 209.9 Mb (ftp)(http) BIGWIG
GSE185921_IgG24_merged.bigwig 130.7 Mb (ftp)(http) BIGWIG
GSE185921_IgG25_merged.bigwig 164.7 Mb (ftp)(http) BIGWIG
GSE185921_IgG34_merged.bigwig 89.2 Mb (ftp)(http) BIGWIG
GSE185921_IgG67_merged.bigwig 176.9 Mb (ftp)(http) BIGWIG
GSE185921_RAW.tar 10.1 Gb (http)(custom) TAR (of BED, BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap