PMID- 34878533
OWN - NLM
STAT- MEDLINE
DCOM- 20220308
LR  - 20220308
IS  - 1756-2651 (Electronic)
IS  - 0021-924X (Linking)
VI  - 171
IP  - 3
DP  - 2022 Mar 3
TI  - Long noncoding RNAs transcribed downstream of the human beta-globin locus regulate 
      beta-globin gene expression.
PG  - 287-294
LID - 10.1093/jb/mvab130 [doi]
AB  - The five beta-like globin genes (epsilon, Ggamma, Agamma, delta and beta) at the human beta-globin gene 
      locus are known to be expressed at specific developmental stages, although 
      details of the underlying mechanism remain to be uncovered. Here we used an in 
      vitro transcription assay to clarify the mechanisms that control this gene 
      expression. We first tested nuclear RNA from HeLa cells using RT-qPCR and 
      discovered a long noncoding RNAs (lncRNAs) within a 5.2-kb region beginning 
      4.4 kb downstream of the beta-globin gene coding region. We investigated nuclear RNA 
      from K562 cells using a primer-extension assay and determined the transcription 
      start sites (TSSs) of these lncRNAs. To clarify their functional role, we 
      performed knockdown (KD) of these lncRNAs in K562 cells. Hydroxyurea (HU), which 
      induces differentiation of K562 cells, increased haemoglobin peptide production, 
      and the effect was enhanced by KD of these lncRNAs, which also enhanced 
      upregulation of the gamma-globin expression induced by HU. To confirm these results, 
      we performed an in vitro transcription assay. Noncoding single-stranded RNAs 
      inhibited beta-globin expression, which was upregulated by GATA1. Furthermore, 
      lncRNAs interacted with GATA1 without sequence specificity and inhibited its 
      binding to its target DNA response element in vitro. Our results suggest that 
      lncRNAs downstream of the beta-globin gene locus are key factors regulating globin 
      gene expression.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Japanese Biochemical Society. All rights reserved.
FAU - Higashi, Miki
AU  - Higashi M
AD  - Department of Biochemistry, Nagasaki University Graduate School of Biomedical 
      Sciences, Nagasaki, Japan.
AD  - Department of Physiology, Saitama Medical University, Saitama, Japan.
FAU - Ikehara, Tsuyoshi
AU  - Ikehara T
AD  - Department of Biochemistry, Nagasaki University Graduate School of Biomedical 
      Sciences, Nagasaki, Japan.
AD  - Department of Food Science and Technology, National Fisheries University, 
      Yamaguchi, Japan.
FAU - Nakagawa, Takeya
AU  - Nakagawa T
AD  - Department of Biochemistry, Nagasaki University Graduate School of Biomedical 
      Sciences, Nagasaki, Japan.
FAU - Yoneda, Mitsuhiro
AU  - Yoneda M
AD  - Department of Biochemistry, Nagasaki University Graduate School of Biomedical 
      Sciences, Nagasaki, Japan.
FAU - Hattori, Naoko
AU  - Hattori N
AD  - Department of Biochemistry, Nagasaki University Graduate School of Biomedical 
      Sciences, Nagasaki, Japan.
FAU - Ikeda, Masaaki
AU  - Ikeda M
AD  - Department of Physiology, Saitama Medical University, Saitama, Japan.
FAU - Ito, Takashi
AU  - Ito T
AD  - Department of Biochemistry, Nagasaki University Graduate School of Biomedical 
      Sciences, Nagasaki, Japan.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Biochem
JT  - Journal of biochemistry
JID - 0376600
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (beta-Globins)
RN  - 0 (gamma-Globins)
SB  - IM
MH  - Gene Expression
MH  - HeLa Cells
MH  - Humans
MH  - *RNA, Long Noncoding/genetics
MH  - beta-Globins/genetics
MH  - gamma-Globins/genetics/metabolism
OTO - NOTNLM
OT  - human beta-globin gene locus
OT  - in vitro transcription assay
OT  - noncoding transcripts
OT  - gamma-globin
EDAT- 2021/12/09 06:00
MHDA- 2022/03/09 06:00
CRDT- 2021/12/08 12:24
PHST- 2021/04/02 00:00 [received]
PHST- 2021/11/07 00:00 [accepted]
PHST- 2021/12/09 06:00 [pubmed]
PHST- 2022/03/09 06:00 [medline]
PHST- 2021/12/08 12:24 [entrez]
AID - 6456259 [pii]
AID - 10.1093/jb/mvab130 [doi]
PST - ppublish
SO  - J Biochem. 2022 Mar 3;171(3):287-294. doi: 10.1093/jb/mvab130.