PMID- 32457812
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220813
IS  - 1747-0862 (Print)
IS  - 1747-0862 (Electronic)
IS  - 1747-0862 (Linking)
VI  - 13
IP  - 3
DP  - 2019
TI  - Highly Variable Expression of ESR1 Splice Variants in Human Liver: Implication in 
      the Liver Gene Expression Regulation and Inter-Person Variability in Drug 
      Metabolism and Liver Related Diseases.
LID - 434 [pii]
AB  - Estrogen receptor alpha (ESR1) plays an important role in many tissues including 
      the liver. Numerous alternative splice variants of ESR1 exist that encode ESR1 
      proteins with varying functions. We aim to study ESR1 genomic organization and 
      its mRNA expression profile in human liver by incorporating information from 
      literature and genomic databases (Ensembl, NCBI and GTEx), and employing a 
      quantitative method to measure all known ESR1 mRNA splice variants in 36 human 
      livers. We re-constructed ESR1 genomic organization map that contains 29 exons. 
      ESR1 mRNA splice variants with varying 5' untranslated region (5'UTR) and/or 
      missing each of eight coding exons are readily detectable in liver and other 
      tissues. Moreover, we found extensive inter-individual variability in splice 
      variant pattern of ESR1 transcripts. Specifically, ESR1 transcripts lacking first 
      coding exon are the main transcripts in liver, which encode ESR1 proteins missing 
      N-terminal 173 amino acids (for example, ERalpha46), reported previously to have 
      either constitutive activity or dominant negative effects depending on cellular 
      context. Moreover, some livers predominantly express ESR1 transcripts missing 
      exon 10 or 16, encoding C-terminal truncated ESR1 proteins with varying ESR1 
      activities. Inter-person variability in ESR1 expression profile may contribute to 
      inter-person variability in drug metabolism and susceptibility to liver related 
      diseases.
FAU - Sun, J W
AU  - Sun JW
AD  - Department of Biological Chemistry and Pharmacology, College of Medicine, The 
      Ohio State University, Columbus, Ohio, USA.
FAU - Collins, J M
AU  - Collins JM
AD  - Department of Pharmacotherapy and Translational Research, Center for 
      Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, 
      Florida, USA.
FAU - Ling, D
AU  - Ling D
AD  - Department of Pharmacotherapy and Translational Research, Center for 
      Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, 
      Florida, USA.
FAU - Wang, D
AU  - Wang D
AD  - Department of Pharmacotherapy and Translational Research, Center for 
      Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, 
      Florida, USA.
LA  - eng
GR  - R01 GM120396/GM/NIGMS NIH HHS/United States
GR  - R01 HL126969/HL/NHLBI NIH HHS/United States
GR  - R01 MD011307/MD/NIMHD NIH HHS/United States
PT  - Journal Article
DEP - 20190930
PL  - England
TA  - J Mol Genet Med
JT  - Journal of molecular and genetic medicine : an international journal of 
      biomedical research
JID - 101256516
PMC - PMC7249510
MID - NIHMS1067622
OTO - NOTNLM
OT  - (ESR1)
OT  - Alternative splicing
OT  - Gene expression
OT  - Inter-person variability
OT  - Liver
COIS- Conflicts of Interest The authors declared no conflict of interests.
EDAT- 2019/01/01 00:00
MHDA- 2019/01/01 00:01
PMCR- 2020/05/26
CRDT- 2020/05/28 06:00
PHST- 2020/05/28 06:00 [entrez]
PHST- 2019/01/01 00:00 [pubmed]
PHST- 2019/01/01 00:01 [medline]
PHST- 2020/05/26 00:00 [pmc-release]
AID - 434 [pii]
PST - ppublish
SO  - J Mol Genet Med. 2019;13(3):434. Epub 2019 Sep 30.