Impaired placental trophoblast lineage differentiation in Alkbh1-/- mice

被引：72

作者：

Pan, Zishu ^{[1
,2
]}

Sikandar, Shaheen ^{[1
,2
]}

Witherspoon, Mavee ^{[1
,2
]}

Dizon, Diana ^{[1
,2
]}

Nguyen, Terrence ^{[1
]}

Benirschke, Kurt ^{[3
]}

Wiley, Christopher ^{[2
]}

Vrana, Paul ^{[2
]}

Lipkin, Steven M. ^{[1
,2
]}

机构：

[1] Univ Calif Irvine, Dept Med, Irvine, CA 92697 USA

[2] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA

[3] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA

来源：

DEVELOPMENTAL DYNAMICS | 2008年 / 237卷 / 02期

关键词：

placenta trophoblast differentiation; Alkbh1(-/-); AlkB gene family;

D O I：

10.1002/dvdy.21418

中图分类号：

R602 [外科病理学、解剖学]; R32 [人体形态学];

学科分类号：

100101 ;

摘要：

E. coli AlkB has been intensively studied since 1983, but the in vivo roles of its mammalian homologue Alkbh1 are unknown. We, therefore, created null mice for Alkbh1. Alkbh1 mRNA is expressed at highest levels in the trophoblast lineages of the developing placenta. Alkbh1-/- placentas have decreased expression of differentiated trophoblast markers including Tpbp, Gcm1, and Pl-1, and increased expression of the trophoblast stem cell marker Eomes. Alkbh1 localizes to nuclear euchromatin, and interacts strongly with Mrj, an essential placental gene that mediates gene repression by recruitment of class 11 histone deacetylases (HDACs). Competition experiments show Alkbh1 and HDAC4 binding to Mrj are mutually exclusive, which causes decreased HDAC activity and increased target gene expression. Our study demonstrates Alkbh1 performs important functions in placental trophoblast lineage differentiation and participates in mechanisms of transcriptional regulation.

引用

页码：316 / 327

页数：12

共 68 条

[1]

Basyuk E, 1999, DEV DYNAM, V214, P303, DOI 10.1002/(SICI)1097-0177(199904)214:4<303::AID-AJA3>3.3.CO

[2]

2-2

[3] AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism [J].

Begley, TJ ;

Samson, LD .

TRENDS IN BIOCHEMICAL SCIENCES, 2003, 28 (01) :2-5

[4] THE ESCHERICHIA-COLI ALKB PROTEIN PROTECTS HUMAN-CELLS AGAINST ALKYLATION-INDUCED TOXICITY [J].

CHEN, BRJ ;

CARROLL, P ;

SAMSON, L .

JOURNAL OF BACTERIOLOGY, 1994, 176 (20) :6255-6261

[5] Characterization of a brain-enriched chaperone, MRJ, that inhibits huntingtin aggregation and toxicity independently [J].

Chuang, JZ ;

Zhou, H ;

Zhu, M ;

Li, SH ;

Li, XJ ;

Sung, CH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (22) :19831-19838

[6] Developmental dynamics of the definitive mouse placenta assessed by stereology [J].

Coan, PM ;

Ferguson-Smith, AC ;

Burton, GJ .

BIOLOGY OF REPRODUCTION, 2004, 70 (06) :1806-1813

[7] MOLECULAR-CLONING AND EXPRESSION OF MOUSE PLACENTAL LACTOGEN-I COMPLEMENTARY DEOXYRIBONUCLEIC-ACID [J].

COLOSI, P ;

TALAMANTES, F ;

LINZER, DIH .

MOLECULAR ENDOCRINOLOGY, 1987, 1 (11) :767-776

[8] Placental-specific IGF-II is a major modulator of placental and fetal growth [J].

Constância, M ;

Hemberger, M ;

Hughes, J ;

Dean, W ;

Ferguson-Smith, A ;

Fundele, R ;

Stewart, F ;

Kelsey, G ;

Fowden, A ;

Sibley, C ;

Reik, W .

NATURE, 2002, 417 (6892) :945-948

[9] The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment [J].

Dai, YS ;

Xu, J ;

Molkentin, JD .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (22) :9936-9948

[10] AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivo [J].

Delaney, JC ;

Smeester, L ;

Wong, CY ;

Frick, LE ;

Taghizadeh, K ;

Wishnok, JS ;

Drennan, CL ;

Samson, LD ;

Essigmann, JM .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2005, 12 (10) :855-860

← 1 2 3 4 5 6 7 →