Murine DNA cytosine C5-methyltransferase:: in vitro studies of de novo methylation spreading

被引：9

作者：

Aubol, BE ^{[1
]}

Reich, NO ^{[1
]}

机构：

[1] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 310卷 / 01期

关键词：

DNA cytosine methyltransferase; methylation spreading; single stranded DNA; N-terminal domain; Dnmt1;

D O I：

10.1016/j.bbrc.2003.08.138

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The preference of murine DNA (cytosine-5)-methyltransferase (Dnmt1) for single stranded DNA substrates is increased up to 50-fold by the presence of a proximal 5-methyl cytosine (5(me)C). This modulation is distance-dependent and is due to an enhanced binding affinity and minor changes in catalytic efficiency. No modulation was observed with double stranded DNA. Modulation requires that the 5(me)C moiety be attached to the DNA strand containing the CpG methylation target. Our results support a model in which 5(me)C binding by the enzyme occurs to at least one site outside the region involved in CpG recognition. No modulation in response to 5(me)C is observed with the bacterial enzyme M.SssI, which lacks the large N-terminal regulatory domain found in Dnmt1. We suggest that this allosteric modulation involves the N-terminal domain of Dnmt1. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：209 / 214

页数：6

共 35 条

[1] ACTIVATION OF MAMMALIAN DNA METHYLTRANSFERASE BY CLEAVAGE OF A ZN BINDING REGULATORY DOMAIN [J].

BESTOR, TH .

EMBO JOURNAL, 1992, 11 (07) :2611-2617

[2] DNA METHYLATION INHIBITS TRANSCRIPTION INDIRECTLY VIA A METHYL-CPG BINDING-PROTEIN [J].

BOYES, J ;

BIRD, A .

CELL, 1991, 64 (06) :1123-1134

[3] Hairpin induced slippage and hyper-methylation of the fragile X DNA triplets [J].

Chen, X ;

Mariappan, SVS ;

Moyzis, RK ;

Bradbury, EM ;

Gupta, G .

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 1998, 15 (04) :745-756

[4] 5-METHYL-2'-DEOXYCYTIDINE IN SINGLE-STRANDED-DNA CAN ACT IN CIS TO SIGNAL DE-NOVO DNA METHYLATION [J].

CHRISTMAN, JK ;

SHEIKHNEJAD, G ;

MARASCO, CJ ;

SUFRIN, JR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7347-7351

[5] A new concept in (adenoviral) oncogenesis: Integration of foreign DNA and its consequences [J].

Doerfler, W .

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 1996, 1288 (02) :F79-F99

[6] ABOUT MAIZE TRANSPOSABLE ELEMENTS AND DEVELOPMENT [J].

FEDOROFF, NV .

CELL, 1989, 56 (02) :181-191

[7] Murine DNA cytosine-C-5 methyltransferase: Pre-steady- and steady-state kinetic analysis with regulatory DNA sequences [J].

Flynn, J ;

Glickman, JF ;

Reich, NO .

BIOCHEMISTRY, 1996, 35 (23) :7308-7315

[8] Murine DNA (Cytosine-5-)-methyltransferase: Steady-state and substrate trapping analyses of the kinetic mechanism [J].

Flynn, J ;

Reich, N .

BIOCHEMISTRY, 1998, 37 (43) :15162-15169

[9] DNA binding discrimination of the murine DNA cytosine-C5 methyltransferase [J].

Flynn, J ;

Azzam, R ;

Reich, N .

JOURNAL OF MOLECULAR BIOLOGY, 1998, 279 (01) :101-116

[10] Peptide mapping of the murine DNA methyltransferase reveals a major phosphorylation site and the start of translation [J].

Glickman, JF ;

Pavlovich, JG ;

Reich, NO .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (28) :17851-17857

← 1 2 3 4 →