Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1

N. Kalakonda; W. Fischle; P. Boccuni; N. Gurvich; R. Hoya-Arias; X. Zhao; Y. Miyata; D. MacGrogan; J. Zhang; J. K. Sims; J. C. Rice; S. D. Nimer

doi:10.1038/onc.2008.67

Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1

N. Kalakonda, W. Fischle, P. Boccuni, N. Gurvich, R. Hoya-Arias, X. Zhao, Y. Miyata, D. MacGrogan, J. Zhang, J. K. Sims, J. C. Rice, S. D. Nimer

Research output: Contribution to journal › Article › peer-review

124 Scopus citations

Abstract

Lethal 3 malignant brain tumor 1 (L3MBTL1), a homolog of the Drosophila polycomb tumor suppressor l(3)mbt, contains three tandem MBT repeats (3xMBT) that are critical for transcriptional repression. We recently reported that the 3xMBT repeats interact with mono- and dimethylated lysines in the amino termini of histones H4 and H1b to promote methylation-dependent chromatin compaction. Using a series of histone peptides, we now show that the recognition of mono- and dimethylated lysines in histones H3, H4 and H1.4 (but not their trimethylated or unmodified counterparts) by 3xMBT occurs in the context of a basic environment, requiring a conserved aspartic acid (D355) in the second MBT repeat. Despite the broad range of in vitro binding, the chromatin association of L3MBTL1 mirrors the progressive accumulation of H4K20 monomethylation during the cell cycle. Furthermore, transcriptional repression by L3MBTL1 is enhanced by the H4K20 monomethyltransferase PR-SET7 (to which it binds) but not SUV420H1 (an H4K20 trimethylase) or G9a (an H3K9 dimethylase) and knockdown of PR-SET7 decreases H4K20me1 levels and the chromatin association of L3MBTL1. Our studies identify the importance of H4K20 monomethylation and of PR-SET7 for L3MBTL1 function.

Original language	English (US)
Pages (from-to)	4293-4304
Number of pages	12
Journal	Oncogene
Volume	27
Issue number	31
DOIs	https://doi.org/10.1038/onc.2008.67
State	Published - Jul 17 2008
Externally published	Yes

Bibliographical note

Funding Information:
We dedicate this paper to the late Piernicola Boccuni, whose beautiful life as a physician–scientist and as a husband, father and friend, ended far too quickly. This work was made possible by grants from the National Institute of Health (SDN), the Leukemia and Lymphoma Society (SDN,

Keywords

Cell cycle
Chromatin
L3MBTL1
Lysine monomethylation
PR-SET7

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/onc.2008.67

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title = "Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1",

abstract = "Lethal 3 malignant brain tumor 1 (L3MBTL1), a homolog of the Drosophila polycomb tumor suppressor l(3)mbt, contains three tandem MBT repeats (3xMBT) that are critical for transcriptional repression. We recently reported that the 3xMBT repeats interact with mono- and dimethylated lysines in the amino termini of histones H4 and H1b to promote methylation-dependent chromatin compaction. Using a series of histone peptides, we now show that the recognition of mono- and dimethylated lysines in histones H3, H4 and H1.4 (but not their trimethylated or unmodified counterparts) by 3xMBT occurs in the context of a basic environment, requiring a conserved aspartic acid (D355) in the second MBT repeat. Despite the broad range of in vitro binding, the chromatin association of L3MBTL1 mirrors the progressive accumulation of H4K20 monomethylation during the cell cycle. Furthermore, transcriptional repression by L3MBTL1 is enhanced by the H4K20 monomethyltransferase PR-SET7 (to which it binds) but not SUV420H1 (an H4K20 trimethylase) or G9a (an H3K9 dimethylase) and knockdown of PR-SET7 decreases H4K20me1 levels and the chromatin association of L3MBTL1. Our studies identify the importance of H4K20 monomethylation and of PR-SET7 for L3MBTL1 function.",

keywords = "Cell cycle, Chromatin, L3MBTL1, Lysine monomethylation, PR-SET7",

author = "N. Kalakonda and W. Fischle and P. Boccuni and N. Gurvich and R. Hoya-Arias and X. Zhao and Y. Miyata and D. MacGrogan and J. Zhang and Sims, {J. K.} and Rice, {J. C.} and Nimer, {S. D.}",

note = "Funding Information: We dedicate this paper to the late Piernicola Boccuni, whose beautiful life as a physician–scientist and as a husband, father and friend, ended far too quickly. This work was made possible by grants from the National Institute of Health (SDN), the Leukemia and Lymphoma Society (SDN,",

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AU - Fischle, W.

AU - Boccuni, P.

AU - Gurvich, N.

AU - Hoya-Arias, R.

AU - Zhao, X.

AU - Miyata, Y.

AU - MacGrogan, D.

AU - Zhang, J.

AU - Sims, J. K.

AU - Rice, J. C.

AU - Nimer, S. D.

N1 - Funding Information: We dedicate this paper to the late Piernicola Boccuni, whose beautiful life as a physician–scientist and as a husband, father and friend, ended far too quickly. This work was made possible by grants from the National Institute of Health (SDN), the Leukemia and Lymphoma Society (SDN,

PY - 2008/7/17

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N2 - Lethal 3 malignant brain tumor 1 (L3MBTL1), a homolog of the Drosophila polycomb tumor suppressor l(3)mbt, contains three tandem MBT repeats (3xMBT) that are critical for transcriptional repression. We recently reported that the 3xMBT repeats interact with mono- and dimethylated lysines in the amino termini of histones H4 and H1b to promote methylation-dependent chromatin compaction. Using a series of histone peptides, we now show that the recognition of mono- and dimethylated lysines in histones H3, H4 and H1.4 (but not their trimethylated or unmodified counterparts) by 3xMBT occurs in the context of a basic environment, requiring a conserved aspartic acid (D355) in the second MBT repeat. Despite the broad range of in vitro binding, the chromatin association of L3MBTL1 mirrors the progressive accumulation of H4K20 monomethylation during the cell cycle. Furthermore, transcriptional repression by L3MBTL1 is enhanced by the H4K20 monomethyltransferase PR-SET7 (to which it binds) but not SUV420H1 (an H4K20 trimethylase) or G9a (an H3K9 dimethylase) and knockdown of PR-SET7 decreases H4K20me1 levels and the chromatin association of L3MBTL1. Our studies identify the importance of H4K20 monomethylation and of PR-SET7 for L3MBTL1 function.

AB - Lethal 3 malignant brain tumor 1 (L3MBTL1), a homolog of the Drosophila polycomb tumor suppressor l(3)mbt, contains three tandem MBT repeats (3xMBT) that are critical for transcriptional repression. We recently reported that the 3xMBT repeats interact with mono- and dimethylated lysines in the amino termini of histones H4 and H1b to promote methylation-dependent chromatin compaction. Using a series of histone peptides, we now show that the recognition of mono- and dimethylated lysines in histones H3, H4 and H1.4 (but not their trimethylated or unmodified counterparts) by 3xMBT occurs in the context of a basic environment, requiring a conserved aspartic acid (D355) in the second MBT repeat. Despite the broad range of in vitro binding, the chromatin association of L3MBTL1 mirrors the progressive accumulation of H4K20 monomethylation during the cell cycle. Furthermore, transcriptional repression by L3MBTL1 is enhanced by the H4K20 monomethyltransferase PR-SET7 (to which it binds) but not SUV420H1 (an H4K20 trimethylase) or G9a (an H3K9 dimethylase) and knockdown of PR-SET7 decreases H4K20me1 levels and the chromatin association of L3MBTL1. Our studies identify the importance of H4K20 monomethylation and of PR-SET7 for L3MBTL1 function.

KW - Cell cycle

KW - Chromatin

KW - L3MBTL1

KW - Lysine monomethylation

KW - PR-SET7

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VL - 27

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JO - Oncogene

JF - Oncogene

IS - 31

ER -

Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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