All

What are you looking for?

All
Projects
Results
Organizations

Quick search

  • Projects supported by TA ČR
  • Excellent projects
  • Projects with the highest public support
  • Current projects

Smart search

  • That is how I find a specific +word
  • That is how I leave the -word out of the results
  • “That is how I can find the whole phrase”

Dominant-negative SMARCA4 mutants alter the accessibility landscape of tissue-unrestricted enhancers

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00489776" target="_blank" >RIV/61388963:_____/18:00489776 - isvavai.cz</a>

  • Result on the web

    <a href="http://dx.doi.org/10.1038/s41594-017-0007-3" target="_blank" >http://dx.doi.org/10.1038/s41594-017-0007-3</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1038/s41594-017-0007-3" target="_blank" >10.1038/s41594-017-0007-3</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Dominant-negative SMARCA4 mutants alter the accessibility landscape of tissue-unrestricted enhancers

  • Original language description

    Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes, contributes to a range of malignancies and neurologic disorders. Unfortunately, the effects of SMARCA4 missense mutations have remained uncertain. Here we show that SMARCA4 cancer missense mutations target conserved ATPase surfaces and disrupt the mechanochemical cycle of remodeling. We find that heterozygous expression of mutants alters the open chromatin landscape at thousands of sites across the genome. Loss of DNA accessibility does not directly overlap with Polycomb accumulation, but is enriched in 'A compartments' at active enhancers, which lose H3K27ac but not H3K4me1. Affected positions include hundreds of sites identified as superenhancers in many tissues. Dominant-negative mutation induces pro-oncogenic expression changes, including increased expression of Myc and its target genes. Together, our data suggest that disruption of enhancer accessibility represents a key source of altered function in disorders with SMARCA4 mutations in a wide variety of tissues.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    <a href="/en/project/GA16-06357S" target="_blank" >GA16-06357S: Structural basis for the biological function of LEDGF/p75 and HRP-2</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2018

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Nature structural & molecular biology

  • ISSN

    1545-9993

  • e-ISSN

  • Volume of the periodical

    25

  • Issue of the periodical within the volume

    1

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    12

  • Pages from-to

    61-72

  • UT code for WoS article

    000423547700010

  • EID of the result in the Scopus database

    2-s2.0-85042743313