CoChat
Sign Up
PreprintCited by 14Genomics and Chromatin DynamicsChromatin Remodeling and CancerEpigenetics and DNA Methylation

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Clustered PHD domains in KMT2/MLL proteins are attracted by H3K4me3 and H3 acetylation-rich active promoters and enhancers

Open access
Stroynowska-Czerwinska, Anna Maria, Klimczak, Magdalena, Pastor, Michal, Kazrani, Asgar Abbas, Misztal, Katarzyna, Bochtler, Matthias·2021·Cellular and Molecular Life Sciences
DOI 10.1101/2021.10.15.462366PMC PMC9813062

Preprint — published as 10.1007/s00018-022-04651-1 · Paper page

Open this paper in CoChat — free accountOpen PDF

Abstract

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. GRAPHICAL ABSTRACT:

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2021.10.15.462366

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 83

  1. 10.1038/378505a0 · DOI
  2. 10.1016/S1097-2765(02)00741-4 · DOI
  3. 10.1016/j.scr.2010.03.004 · DOI
  4. 10.1128/MCB.00924-09 · DOI
  5. 10.1093/bfgp/els017 · DOI · Paper page
  6. 10.1073/pnas.88.23.10735 · DOI
  7. 10.1016/j.molcel.2014.02.033 · DOI
  8. 10.1016/j.canlet.2019.05.024 · DOI
  9. 10.1016/j.cell.2018.02.060 · DOI · Paper page
  10. 10.1038/nature12634 · DOI · Paper page
  11. 10.1038/s41591-018-0034-6 · DOI
  12. 10.1038/nsmb.1714 · DOI
  13. 10.1016/j.celrep.2020.108200 · DOI
  14. 10.1016/j.cell.2005.03.036 · DOI
  15. 10.1101/gad.201327.112 · DOI · Paper page
  16. 10.1128/MCB.01181-13 · DOI · Paper page
  17. 10.1042/BST20191164 · DOI · Paper page
  18. 10.1038/embor.2011.101 · DOI
  19. 10.1021/acs.biochem.0c00035 · DOI
  20. 10.1038/nsmb1128 · DOI
  21. 10.1038/sj.emboj.7601340 · DOI
  22. 10.1016/j.str.2017.11.022 · DOI
  23. 10.1016/j.bbagrm.2018.10.009 · DOI
  24. 10.1038/321209a0 · DOI · Paper page
  25. 10.1016/j.tibs.2005.11.001 · DOI
  26. 10.1124/mi.9.6.7 · DOI
  27. 10.1038/nature04835 · DOI
  28. 10.1016/j.cell.2010.05.016 · DOI
  29. 10.1093/nar/gkt931 · DOI
  30. 10.1038/nature09139 · DOI
  31. 10.1038/s41467-019-10324-8 · DOI
  32. 10.1038/s41467-018-07906-3 · DOI
  33. 10.1101/gad.203356.112 · DOI
  34. 10.1038/nbt.3157 · DOI
  35. 10.1093/nar/gkx1081 · DOI · Paper page
  36. 10.1101/2022.02.28.482307 · DOI
  37. 10.1186/s13148-020-00863-z · DOI
  38. 10.3390/jdb9010006 · DOI
  39. 10.1093/nar/gky1015 · DOI · Paper page
  40. 10.1016/j.ymeth.2006.05.028 · DOI
  41. 10.1038/nchembio.319 · DOI
  42. 10.1371/journal.pone.0006789 · DOI
  43. 10.1016/j.cbpa.2018.02.004 · DOI
  44. 10.1101/2022.02.21.481373 · DOI
  45. 10.1073/pnas.1016071107 · DOI · Paper page
  46. 10.1186/1471-2164-13-424 · DOI
  47. 10.1016/j.tibs.2020.12.012 · DOI
  48. 10.1038/emboj.2011.295 · DOI
  49. 10.1038/sj.onc.1210618 · DOI
  50. 10.1093/embo-reports/kvf053 · DOI
  51. 10.1038/s41467-020-14950-5 · DOI
  52. 10.1186/s13148-015-0075-3 · DOI
  53. 10.1016/j.gene.2017.06.056 · DOI
  54. 10.1038/nsmb1119 · DOI
  55. 10.1038/nsmb1116 · DOI
  56. 10.1126/sciadv.abf4291 · DOI
  57. 10.1038/nsmb.2093 · DOI
  58. 10.1530/ERC-17-0281 · DOI
  59. 10.1242/dev.076687 · DOI
  60. 10.1016/j.ydbio.2013.05.018 · DOI
  61. 10.1126/science.1235122 · DOI · Paper page
  62. 10.1038/leu.2017.213 · DOI
  63. 10.1038/leu.2013.135 · DOI
  64. 10.1038/s41375-019-0451-7 · DOI
  65. 10.1128/AEM.00844-12 · DOI
  66. 10.1038/nmeth1010 · DOI
  67. 10.7554/eLife.21856 · DOI
  68. 10.1093/nar/gkab038 · DOI
  69. 10.1093/nar/gky379 · DOI · Paper page
  70. 10.1038/nmeth.1923 · DOI · Paper page
  71. 10.1186/gb-2008-9-9-r137 · DOI · Paper page
  72. 10.1038/nprot.2012.101 · DOI
  73. 10.1093/nar/gkw257 · DOI · Paper page
  74. 10.1038/nbt.1754 · DOI · Paper page
  75. 10.1093/nar/28.1.27 · DOI · Paper page
  76. 10.1093/nar/gky1055 · DOI · Paper page
  77. 10.1093/nar/gkz332 · DOI
  78. 10.1186/s12859-019-3118-5 · DOI
  79. 10.1093/bioinformatics/btq033 · DOI · Paper page
  80. 10.1186/s12859-017-1708-7 · DOI
  81. 10.1093/nar/gkaa1100 · DOI · Paper page
  82. 10.1093/bioinformatics/btl158 · DOI
  83. 10.1038/msb.2011.75 · DOI

Metadata

Authors
Stroynowska-Czerwinska, A. M., Klimczak, M., Pastor, M., Kazrani, A. A., Misztal, K., & Bochtler, M.
Affiliations
  • International Institute of Molecular and Cell Biology (PL)
  • Institut de génétique et de biologie moléculaire et cellulaire (FR)
Corresponding author
Bochtler, Matthias
ORCID
Venue
Cellular and Molecular Life Sciences
Publisher
openRxiv
Published
2021-10-15
Volume
80
Issue
1
Pages
23-23
ISSN
1420-682X (ISSN-L)
DOI
10.1101/2021.10.15.462366
PMC
PMC9813062
OpenAlex
W4313543515
Cited by
14
References
1
Citations by year
2026: 2 · 2025: 4 · 2024: 6 · 2023: 2
FWCI
1.24
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cellular and Molecular Life Sciences (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Narodowe Centrum Nauki (UMO-2014/14/M/NZ5/00558)
  • Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
  • Instytut Biologii Doswiadczalnej im. M. Nenckiego PAN
  • Międzynarodowy Instytut Biologii Molekularnej i Komórkowej w Warszawie
  • Narodowa Agencja Wymiany Akademickiej (PPI/APM/2018/1/00034)
  • Institute of Molecular and Cell Biology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
plant homeodomain, H3K4me3, histone H3 acetylation, enhancers, CXXC domain, histone lysine methyltransferase, cancer mutations
MeSH terms
PHD Zinc Fingers, Acetylation, Histones, Humans, Leukemia, Neoplasms

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review