Al Gahtany, Mubarak

Gurusamy, Narasimman

Hosoda, Toru

Karunakaran, Gauthaman

Kim, Junghyun

Leri, Annarosa

BMC Genomics

Narasimman Gurusamy

Junghyun Kim

Toru Hosoda

Gauthaman Karunakaran

Mubarak Al Gahtany

Annarosa Leri

Springer - Publisher Connector

POSTER PRESENTATION Open Access
Smyd3, a histone methyltransferase, modulates
the growth and differentiation of human cardiac
stem cells
Narasimman Gurusamy1*, Junghyun Kim2, Toru Hosoda2, Gauthaman Karunakaran1, Mubarak Al Gahtany1,
Annarosa Leri2
From 2nd International Genomic Medical Conference (IGMC 2013)
Jeddah, Kingdom of Saudi Arabia. 24-27 November 2013
Background
The phenotypic properties of embryonic and adult stem
cells are largely mediated by epigenetic modifications which
control stemness, multipotentiality and fate specification. In
this study, our objective was to identify the epigenetic
mechanism regulating the growth and differentiation of
human cardiac stem cells (hCSCs).
Materials and methods
Discarded surgical specimens were enzymatically
digested and c-kit-positive hCSCs were sorted by FACS.
Results
Genome-wide analysis of histone modifications docu-
mented that adult hCSCs are characterized by a bivalent
chromatin configuration similar to that of embryonic
stem cells with repressive and activating marks at lysine
residues of histones H3 and H4. The high levels of
di-(H3K4me2) and tri-methylation (H3K4me3) at lysine
4 of histone H3 prompted us to test the function of his-
tone methyltransferase Smyd3, which is downregulated
by the non-functional mutation in the c-kit receptor, in
hCSCs. Inhibition of Smyd3 by siRNA strategy decreased
the fraction (60%) of cycling hCSCs and increased apop-
tosis (2.5-fold). Attenuation of hCSC growth was coupled
with a decline in the expression of telomerase, hTERT,
and the myocyte specific transcription factors hNkx2.5
and hGata6. By immunolabeling, Smyd3 co-localized
with hTERT, hNkx2.5 and hGATA6 in hCSC nuclei.
Conversely, transfection of hCSCs with a plasmid
carrying Smyd3 was coupled with upregulation of hTERT
and hNkx2.5. Chromatin immunoprecipitation assay
show that Smyd3 binds to hTERT, hGata6 and hNkx2.5
promoter regions that contains the putative binding sites
for Smyd3. Moreover, the mutations at the Smyd3 DNA
binding sites, decreased the promoter activity of hTERT
and hGata6. Smyd3 siRNA treatment decreased the
reporter activity of luciferase reporter plasmids contain-
ing hTERT.
Conclusions
Our results show that Smyd3 represents a crucial epige-
netic modulator of hCSC commitment to the myocyte
lineage.
Authors’ details
1Department of Pharmacology, College of Pharmacy, King Khalid University,
Abha, Kingdom of Saudi Arabia. 2Department of Anesthesia and Medicine,
Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
Published: 2 April 2014
doi:10.1186/1471-2164-15-S2-P69
Cite this article as: Gurusamy et al.: Smyd3, a histone methyltransferase,
modulates the growth and differentiation of human cardiac stem cells.
BMC Genomics 2014 15(Suppl 2):P69.
* Correspondence: gurunaras@gmail.com
1Department of Pharmacology, College of Pharmacy, King Khalid University,
Abha, Kingdom of Saudi Arabia
Full list of author information is available at the end of the article
Gurusamy et al. BMC Genomics 2014, 15(Suppl 2):P69
http://www.biomedcentral.com/1471-2164/15/S2/P69
© 2014 Gurusamy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.


Smyd3, a histone methyltransferase, modulates the growth and differentiation of human cardiac stem cells

Harvard University - DASH 

 Smyd3, a histone methyltransferase, modulates the growth anddifferentiation of human cardiac stem cells  (Article begins on next page)The Harvard community has made this article openly available.Please share how this access benefits you. Your story matters.Citation Gurusamy, Narasimman, Junghyun Kim, Toru Hosoda,Gauthaman Karunakaran, Mubarak Al Gahtany, and AnnarosaLeri. 2014. “Smyd3, a histone methyltransferase, modulates thegrowth and differentiation of human cardiac stem cells.” BMCGenomics 15 (Suppl 2): P69. doi:10.1186/1471-2164-15-S2-P69. http://dx.doi.org/10.1186/1471-2164-15-S2-P69.Published Version doi:10.1186/1471-2164-15-S2-P69Accessed February 16, 2015 4:46:50 PM ESTCitable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717598Terms of Use This article was downloaded from Harvard University's DASHrepository, and is made available under the terms and conditionsapplicable to Other Posted Material, as set forth athttp://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAAPOSTER PRESENTATION Open AccessSmyd3, a histone methyltransferase, modulatesthe growth and differentiation of human cardiacstem cellsNarasimman Gurusamy1*, Junghyun Kim2, Toru Hosoda2, Gauthaman Karunakaran1, Mubarak Al Gahtany1,Annarosa Leri2From 2nd International Genomic Medical Conference (IGMC 2013)Jeddah, Kingdom of Saudi Arabia. 24-27 November 2013BackgroundThe phenotypic properties of embryonic and adult stemcells are largely mediated by epigenetic modifications whichcontrol stemness, multipotentiality and fate specification. Inthis study, our objective was to identify the epigeneticmechanism regulating the growth and differentiation ofhuman cardiac stem cells (hCSCs).Materials and methodsDiscarded surgical specimens were enzymaticallydigested and c-kit-positive hCSCs were sorted by FACS.ResultsGenome-wide analysis of histone modifications docu-mented that adult hCSCs are characterized by a bivalentchromatin configuration similar to that of embryonicstem cells with repressive and activating marks at lysineresidues of histones H3 and H4. The high levels ofdi-(H3K4me2) and tri-methylation (H3K4me3) at lysine4 of histone H3 prompted us to test the function of his-tone methyltransferase Smyd3, which is downregulatedby the non-functional mutation in the c-kit receptor, inhCSCs. Inhibition of Smyd3 by siRNA strategy decreasedthe fraction (60%) of cycling hCSCs and increased apop-tosis (2.5-fold). Attenuation of hCSC growth was coupledwith a decline in the expression of telomerase, hTERT,and the myocyte specific transcription factors hNkx2.5and hGata6. By immunolabeling, Smyd3 co-localizedwith hTERT, hNkx2.5 and hGATA6 in hCSC nuclei.Conversely, transfection of hCSCs with a plasmidcarrying Smyd3 was coupled with upregulation of hTERTand hNkx2.5. Chromatin immunoprecipitation assayshow that Smyd3 binds to hTERT, hGata6 and hNkx2.5promoter regions that contains the putative binding sitesfor Smyd3. Moreover, the mutations at the Smyd3 DNAbinding sites, decreased the promoter activity of hTERTand hGata6. Smyd3 siRNA treatment decreased thereporter activity of luciferase reporter plasmids contain-ing hTERT.ConclusionsOur results show that Smyd3 represents a crucial epige-netic modulator of hCSC commitment to the myocytelineage.Authors’ details1Department of Pharmacology, College of Pharmacy, King Khalid University,Abha, Kingdom of Saudi Arabia.2Department of Anesthesia and Medicine,Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.Published: 2 April 2014doi:10.1186/1471-2164-15-S2-P69Cite this article as: Gurusamy et al.: Smyd3, a histone methyltransferase,modulates the growth and differentiation of human cardiac stem cells.BMC Genomics 2014 15(Suppl 2):P69.* Correspondence: gurunaras@gmail.com1Department of Pharmacology, College of Pharmacy, King Khalid University,Abha, Kingdom of Saudi ArabiaFull list of author information is available at the end of the articleGurusamy et al. BMC Genomics 2014, 15(Suppl 2):P69http://www.biomedcentral.com/1471-2164/15/S2/P69© 2014 Gurusamy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

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Smyd3, a histone methyltransferase, modulates the growth and differentiation of human cardiac stem cells

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