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 Devjournal_title
Genes & developmentauthors
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 Tdoi
10.1101/gad.476008subject
Has Abstractpub_date
2008-08-01 00:00:00pages
2048-61issue
15eissn
0890-9369issn
1549-5477pii
22/15/2048journal_volume
22pub_type
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