NDLI: ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation

Please wait, while we are loading the content...

ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation

Content Provider	Scilit
Author	Clarke, Christopher J. Shamseddine, Achraf A. Jacob, Joseph J. Khalife, Gabrielle Burns, Tara A. Hannun, Yusuf A.
Copyright Year	2016
Description	Journal: Journal of lipid research Neutral sphingomyelinase-2 (nSMase2) is a key ceramide-producing enzyme in cellular stress responses. While many posttranslational regulators of nSMase2 are known, emerging evidence suggests a more protracted regulation of nSMase2 at the transcriptional level. Previously, we reported that nSMase2 is induced by all-trans retinoic acid (ATRA) in MCF7 cells and implicated nSMase2 in ATRA-induced growth arrest. Here, we further investigated how ATRA regulates nSMase2. We find that ATRA regulates nSMase2 transcriptionally through the retinoic acid receptor-α, but this is independent of previously identified transcriptional regulators of nSMase2 (Sp1, Sp3, Runx2) and is not through increased promoter activity. Epigenetically, the nSMase2 gene is not repressively methylated in MCF7 cells. However, inhibition of histone deacetylases (HDACs) with trichostatin A (TSA) induced nSMase2 comparably to ATRA; furthermore, combined ATRA and TSA treatment was not additive, suggesting ATRA regulates nSMase2 through direct modulation of histone acetylation. Confirming this, the histone acetyltransferases CREB-binding protein and p300 were required for ATRA induction of nSMase2. Finally, use of class-specific HDAC inhibitors suggested that HDAC4 and/or HDAC5 are negative regulators of nSMase2 expression. Collectively, these results identify a novel pathway of nSMase2 regulation and suggest that physiological or pharmacological modulation of histone acetylation can directly affect nSMase2 levels.
Related Links	http://www.jlr.org/content/57/5/868.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847633/pdf
Ending Page	881
Page Count	14
Starting Page	868
ISSN	00222275
e-ISSN	15397262
DOI	10.1194/jlr.m067447
Journal	Journal of lipid research
Issue Number	5
Volume Number	57
Language	English
Publisher	Elsevier BV
Publisher Date	2016-05-01
Access Restriction	Open
Subject Keyword	Journal: Journal of lipid research Biochemistry and Molecular Biology All-trans Retinoic Acid Histone Acetyltransferase Histone Deacetylase Neutral Sphingomyelinase-2 Nuclear Receptors Signal Transduction
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Endocrinology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in