PMID- 34922943
OWN - NLM
STAT- MEDLINE
DCOM- 20220428
LR  - 20220531
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 298
IP  - 1
DP  - 2022 Jan
TI  - DNA demethylase ALKBH1 promotes adipogenic differentiation via regulation of 
      HIF-1 signaling.
PG  - 101499
LID - S0021-9258(21)01309-0 [pii]
LID - 10.1016/j.jbc.2021.101499 [doi]
LID - 101499
AB  - DNA N6-adenine methylation (6mA), as a novel adenine modification existing in 
      eukaryotes, shows essential functions in embryogenesis and mitochondrial 
      transcriptions. ALKBH1 is a demethylase of 6mA and plays critical roles in 
      osteogenesis, tumorigenesis, and adaptation to stress. However, the integrated 
      biological functions of ALKBH1 still require further exploration. Here, we 
      demonstrate that knockdown of ALKBH1 inhibits adipogenic differentiation in both 
      human mesenchymal stem cells (hMSCs) and 3T3-L1 preadipocytes, while 
      overexpression of ALKBH1 leads to increased adipogenesis. Using a combination of 
      RNA-seq and N6-mA-DNA-IP-seq analyses, we identify hypoxia-inducible factor-1 
      (HIF-1) signaling as a crucial downstream target of ALKBH1 activity. Depletion of 
      ALKBH1 leads to hypermethylation of both HIF-1alpha and its downstream target GYS1. 
      Simultaneous overexpression of HIF-1alpha and GYS1 restores the adipogenic commitment 
      of ALKBH1-deficient cells. Taken together, our data indicate that ALKBH1 is 
      indispensable for adipogenic differentiation, revealing a novel epigenetic 
      mechanism that regulates adipogenesis.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Liu, Yuting
AU  - Liu Y
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
FAU - Chen, Yaqian
AU  - Chen Y
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
FAU - Wang, Yuan
AU  - Wang Y
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
FAU - Jiang, Shuang
AU  - Jiang S
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
FAU - Lin, Weimin
AU  - Lin W
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
FAU - Wu, Yunshu
AU  - Wu Y
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
FAU - Li, Qiwen
AU  - Li Q
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
FAU - Guo, Yuchen
AU  - Guo Y
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
FAU - Liu, Weiqing
AU  - Liu W
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
FAU - Yuan, Quan
AU  - Yuan Q
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. 
      Electronic address: yuanquan@scu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211217
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 9007-49-2 (DNA)
RN  - EC 1.14.11.33 (ALKBH1 protein, human)
RN  - EC 1.14.11.33 (AlkB Homolog 1, Histone H2a Dioxygenase)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adenine/metabolism
MH  - Adipocytes/cytology/metabolism
MH  - *Adipogenesis
MH  - *AlkB Homolog 1, Histone H2a Dioxygenase/genetics/metabolism
MH  - Animals
MH  - Cell Differentiation
MH  - DNA/metabolism
MH  - DNA Methylation
MH  - Humans
MH  - *Hypoxia-Inducible Factor 1/metabolism
MH  - Mice
MH  - *Osteogenesis
PMC - PMC8760519
OTO - NOTNLM
OT  - ALKBH1
OT  - DNA N6-adenine demethylase
OT  - HIF-1
OT  - adipogenesis
OT  - mesenchymal stem cells
COIS- Conflicts of interest The authors declare that they have no conflicts of interest 
      with the contents of this article.
EDAT- 2021/12/20 06:00
MHDA- 2022/04/29 06:00
PMCR- 2021/12/17
CRDT- 2021/12/19 20:43
PHST- 2021/11/06 00:00 [received]
PHST- 2021/12/04 00:00 [revised]
PHST- 2021/12/08 00:00 [accepted]
PHST- 2021/12/20 06:00 [pubmed]
PHST- 2022/04/29 06:00 [medline]
PHST- 2021/12/19 20:43 [entrez]
PHST- 2021/12/17 00:00 [pmc-release]
AID - S0021-9258(21)01309-0 [pii]
AID - 101499 [pii]
AID - 10.1016/j.jbc.2021.101499 [doi]
PST - ppublish
SO  - J Biol Chem. 2022 Jan;298(1):101499. doi: 10.1016/j.jbc.2021.101499. Epub 2021 
      Dec 17.