A chromatin-wide transition to H4K20 monomethylation impairs genome integrity and programmed DNA rearrangements in the mouse.

Abstract:

:H4K20 methylation is a broad chromatin modification that has been linked with diverse epigenetic functions. Several enzymes target H4K20 methylation, consistent with distinct mono-, di-, and trimethylation states controlling different biological outputs. To analyze the roles of H4K20 methylation states, we generated conditional null alleles for the two Suv4-20h histone methyltransferase (HMTase) genes in the mouse. Suv4-20h-double-null (dn) mice are perinatally lethal and have lost nearly all H4K20me3 and H4K20me2 states. The genome-wide transition to an H4K20me1 state results in increased sensitivity to damaging stress, since Suv4-20h-dn chromatin is less efficient for DNA double-strand break (DSB) repair and prone to chromosomal aberrations. Notably, Suv4-20h-dn B cells are defective in immunoglobulin class-switch recombination, and Suv4-20h-dn deficiency impairs the stem cell pool of lymphoid progenitors. Thus, conversion to an H4K20me1 state results in compromised chromatin that is insufficient to protect genome integrity and to process a DNA-rearranging differentiation program in the mouse.

journal_name

Genes Dev

journal_title

Genes & development

authors

Schotta G,Sengupta R,Kubicek S,Malin S,Kauer M,Callén E,Celeste A,Pagani M,Opravil S,De La Rosa-Velazquez IA,Espejo A,Bedford MT,Nussenzweig A,Busslinger M,Jenuwein T

doi

10.1101/gad.476008

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

2048-61

issue

15

eissn

0890-9369

issn

1549-5477

pii

22/15/2048

journal_volume

22

pub_type

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