PMID- 22802127
OWN - NLM
STAT- MEDLINE
DCOM- 20130218
LR  - 20211021
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Linking)
VI  - 69
IP  - 24
DP  - 2012 Dec
TI  - The faah gene is the first direct target of estrogen in the testis: role of 
      histone demethylase LSD1.
PG  - 4177-90
LID - 10.1007/s00018-012-1074-6 [doi]
AB  - Estrogen (E(2)) regulates spermatogenesis, yet its direct target genes have not 
      been identified in the testis. Here, we cloned the proximal 5' flanking region of 
      the mouse fatty acid amide hydrolase (faah) gene upstream of the luciferase 
      reporter gene, and demonstrated its promoter activity and E(2) inducibility in 
      primary mouse Sertoli cells. Specific mutations in the E(2) response elements 
      (ERE) of the faah gene showed that two proximal ERE sequences (ERE2/3) are 
      essential for E(2)-induced transcription, and chromatin immunoprecipitation 
      experiments showed that E(2) induced estrogen receptor beta binding at ERE2/3 sites 
      in the faah promoter in vivo. Moreover, the histone demethylase LSD1 was found to 
      be associated with ERE2/3 sites and to play a role in mediating E(2) induction of 
      FAAH expression. E(2) induced epigenetic modifications at the faah proximal 
      promoter compatible with transcriptional activation by remarkably decreasing 
      methylation of both DNA at CpG site and histone H3 at lysine 9. Finally, FAAH 
      silencing abolished E(2) protection against apoptosis induced by the FAAH 
      substrate anandamide. Taken together, our results identify FAAH as the first 
      direct target of E(2).
FAU - Grimaldi, Paola
AU  - Grimaldi P
AD  - Department of Public Health and Cellular Biology, University of Rome Tor Vergata, 
      00133 Rome, Italy. paola.grimaldi@uniroma2.it
FAU - Pucci, Mariangela
AU  - Pucci M
FAU - Di Siena, Sara
AU  - Di Siena S
FAU - Di Giacomo, Daniele
AU  - Di Giacomo D
FAU - Pirazzi, Valentina
AU  - Pirazzi V
FAU - Geremia, Raffaele
AU  - Geremia R
FAU - Maccarrone, Mauro
AU  - Maccarrone M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120717
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Estrogens)
RN  - 0 (Histones)
RN  - EC 1.14.11.- (Histone Demethylases)
RN  - EC 1.14.11.- (KDM1a protein, mouse)
RN  - EC 1.5.- (Oxidoreductases, N-Demethylating)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.- (fatty-acid amide hydrolase)
SB  - IM
MH  - Amidohydrolases/chemistry/*genetics/physiology
MH  - Animals
MH  - Apoptosis
MH  - Base Sequence
MH  - DNA Methylation/drug effects
MH  - Estrogen Receptor beta/metabolism/physiology
MH  - Estrogens/*pharmacology
MH  - *Gene Expression Regulation
MH  - Histone Demethylases
MH  - Histones/metabolism
MH  - Male
MH  - Methylation
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oxidoreductases, N-Demethylating/genetics/metabolism/*physiology
MH  - Promoter Regions, Genetic
MH  - Sertoli Cells/drug effects/*metabolism
EDAT- 2012/07/18 06:00
MHDA- 2013/02/19 06:00
CRDT- 2012/07/18 06:00
PHST- 2011/12/12 00:00 [received]
PHST- 2012/06/21 00:00 [accepted]
PHST- 2012/06/19 00:00 [revised]
PHST- 2012/07/18 06:00 [entrez]
PHST- 2012/07/18 06:00 [pubmed]
PHST- 2013/02/19 06:00 [medline]
AID - 10.1007/s00018-012-1074-6 [doi]
PST - ppublish
SO  - Cell Mol Life Sci. 2012 Dec;69(24):4177-90. doi: 10.1007/s00018-012-1074-6. Epub 
      2012 Jul 17.