G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis
Proliferating progenitor cells undergo changes in competence to give rise to post-mitotic progeny of specialized function. These cell-fate transitions typically involve dynamic regulation of gene expression by histone methyltransferase (HMT) complexes. However, the composition, roles, and regulation...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2016-09-01
|
Series: | Stem Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671116301047 |
id |
doaj-dee9e35879264fc6ad3ab9eb6f68e846 |
---|---|
record_format |
Article |
spelling |
doaj-dee9e35879264fc6ad3ab9eb6f68e8462020-11-24T22:57:22ZengElsevierStem Cell Reports2213-67112016-09-017345447010.1016/j.stemcr.2016.06.012G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during NeurogenesisJonathan B. Olsen0Loksum Wong1Steven Deimling2Amanda Miles3Hongbo Guo4Yue Li5Zhaolei Zhang6Jack F. Greenblatt7Andrew Emili8Vincent Tropepe9Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5, CanadaDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, CanadaDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, CanadaDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, CanadaDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, CanadaDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G5, CanadaProliferating progenitor cells undergo changes in competence to give rise to post-mitotic progeny of specialized function. These cell-fate transitions typically involve dynamic regulation of gene expression by histone methyltransferase (HMT) complexes. However, the composition, roles, and regulation of these assemblies in regulating cell-fate decisions in vivo are poorly understood. Using unbiased affinity purification and mass spectrometry, we identified the uncharacterized C2H2-like zinc finger protein ZNF644 as a G9a/GLP-interacting protein and co-regulator of histone methylation. In zebrafish, functional characterization of ZNF644 orthologs, znf644a and znf644b, revealed complementary roles in regulating G9a/H3K9me2-mediated gene silencing during neurogenesis. The non-overlapping requirements for znf644a and znf644b during retinal differentiation demarcate critical aspects of retinal differentiation programs regulated by differential G9a-ZNF644 associations, such as transitioning proliferating progenitor cells toward differentiation. Collectively, our data point to ZNF644 as a critical co-regulator of G9a/H3K9me2-mediated gene silencing during neuronal differentiation.http://www.sciencedirect.com/science/article/pii/S2213671116301047 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jonathan B. Olsen Loksum Wong Steven Deimling Amanda Miles Hongbo Guo Yue Li Zhaolei Zhang Jack F. Greenblatt Andrew Emili Vincent Tropepe |
spellingShingle |
Jonathan B. Olsen Loksum Wong Steven Deimling Amanda Miles Hongbo Guo Yue Li Zhaolei Zhang Jack F. Greenblatt Andrew Emili Vincent Tropepe G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis Stem Cell Reports |
author_facet |
Jonathan B. Olsen Loksum Wong Steven Deimling Amanda Miles Hongbo Guo Yue Li Zhaolei Zhang Jack F. Greenblatt Andrew Emili Vincent Tropepe |
author_sort |
Jonathan B. Olsen |
title |
G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis |
title_short |
G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis |
title_full |
G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis |
title_fullStr |
G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis |
title_full_unstemmed |
G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis |
title_sort |
g9a and znf644 physically associate to suppress progenitor gene expression during neurogenesis |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2016-09-01 |
description |
Proliferating progenitor cells undergo changes in competence to give rise to post-mitotic progeny of specialized function. These cell-fate transitions typically involve dynamic regulation of gene expression by histone methyltransferase (HMT) complexes. However, the composition, roles, and regulation of these assemblies in regulating cell-fate decisions in vivo are poorly understood. Using unbiased affinity purification and mass spectrometry, we identified the uncharacterized C2H2-like zinc finger protein ZNF644 as a G9a/GLP-interacting protein and co-regulator of histone methylation. In zebrafish, functional characterization of ZNF644 orthologs, znf644a and znf644b, revealed complementary roles in regulating G9a/H3K9me2-mediated gene silencing during neurogenesis. The non-overlapping requirements for znf644a and znf644b during retinal differentiation demarcate critical aspects of retinal differentiation programs regulated by differential G9a-ZNF644 associations, such as transitioning proliferating progenitor cells toward differentiation. Collectively, our data point to ZNF644 as a critical co-regulator of G9a/H3K9me2-mediated gene silencing during neuronal differentiation. |
url |
http://www.sciencedirect.com/science/article/pii/S2213671116301047 |
work_keys_str_mv |
AT jonathanbolsen g9aandznf644physicallyassociatetosuppressprogenitorgeneexpressionduringneurogenesis AT loksumwong g9aandznf644physicallyassociatetosuppressprogenitorgeneexpressionduringneurogenesis AT stevendeimling g9aandznf644physicallyassociatetosuppressprogenitorgeneexpressionduringneurogenesis AT amandamiles g9aandznf644physicallyassociatetosuppressprogenitorgeneexpressionduringneurogenesis AT hongboguo g9aandznf644physicallyassociatetosuppressprogenitorgeneexpressionduringneurogenesis AT yueli g9aandznf644physicallyassociatetosuppressprogenitorgeneexpressionduringneurogenesis AT zhaoleizhang g9aandznf644physicallyassociatetosuppressprogenitorgeneexpressionduringneurogenesis AT jackfgreenblatt g9aandznf644physicallyassociatetosuppressprogenitorgeneexpressionduringneurogenesis AT andrewemili g9aandznf644physicallyassociatetosuppressprogenitorgeneexpressionduringneurogenesis AT vincenttropepe g9aandznf644physicallyassociatetosuppressprogenitorgeneexpressionduringneurogenesis |
_version_ |
1725651104461488128 |