KMT2B Is Selectively Required for Neuronal Transdifferentiation, and Its Loss Exposes Dystonia Candidate Genes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F18%3A10381529" target="_blank" >RIV/00064165:_____/18:10381529 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/18:10381529

Result on the web

<a href="https://doi.org/10.1016/j.celrep.2018.09.067" target="_blank" >https://doi.org/10.1016/j.celrep.2018.09.067</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.celrep.2018.09.067" target="_blank" >10.1016/j.celrep.2018.09.067</a>

Result language

angličtina

Original language name

KMT2B Is Selectively Required for Neuronal Transdifferentiation, and Its Loss Exposes Dystonia Candidate Genes

Original language description

Transdifferentiation of fibroblasts into induced neuronal cells (iNs) by the neuron-specific transcription factors Brn2, Myt1l, and Ascl1 is a paradigmatic example of inter-lineage conversion across epigenetically distant cells. Despite tremendous progress regarding the transcriptional hierarchy underlying transdifferentiation, the enablers of the concomitant epigenome resetting remain to be elucidated. Here, we investigated the role of KMT2A and KMT2B, two histone H3 lysine 4 methylases with cardinal roles in development, through individual and combined inactivation. We found that Kmt2b, whose human homolog&apos;s mutations cause dystonia, is selectively required for iN conversion through suppression of the alternative myocyte program and induction of neuronal maturation genes. The identification of KMT2B-vulnerable targets allowed us, in turn, to expose, in a cohort of 225 patients, 45 unique variants in 39 KMT2B targets, which represent promising candidates to dissect the molecular bases of dystonia. Barbagiovanni et al. demonstrate that KMT2B, in contrast to KMT2A, is fundamental for the epigenetic and transcriptomic resetting underlying transdifferentiation of fibroblasts into induced neuronal cells (iNs), acting both in the suppression of alternative fates and in the promotion of iN maturation. Transdifferentiation-specific KMT2B targets reveal dystonia-causative gene candidates.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/GA16-13323S" target="_blank" >GA16-13323S: MIcro and MAcro Connectomics of the Subthalamic nucleus in humans: impact of neuromodulation and dopamine depletion</a><br>

Continuities

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

Publication year

2018

Confidentiality

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

Name of the periodical

Cell Reports

ISSN

2211-1247

e-ISSN

—

Volume of the periodical

25

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

988-1001

UT code for WoS article

000448219500016

EID of the result in the Scopus database

2-s2.0-85055106133