Konference: 2007 49th ASH Annual Meeting - účast ČR
Kategorie:
Maligní lymfomy a leukémie
Téma: Publikace ve sborníku
Číslo abstraktu: 4062
Autoři: RNDr. Jarmila Vargová (Podskočová); Mgr. Karina Vargová, Ph.D.; Mgr. Juraj Kokavec; Arthur I. Skoultchi, Ph.D.; Doc. MUDr. Tomáš Stopka, Ph.D.
Snf2h is a chromatin remodeling ATPase which along with associated
factors has the ability to assemble and slide nucleosomes. Snf2h
levels are substantially increased in acute leukemia cells and in
aggressive solid tumors, suggesting a role for Snf2h in regulating
chromatin structure in malignancy. Snf2h-null mice exhibit early
embryonic lethality and Snf2h heterozygous mutant mice are
growth-retarded (Stopka 2003, Chong 2007). In this study we have
used Snf2h hemizygous (+/-) embryonic stem (ES) cells and mice to
examine the consequences of reduced Snf2h stoichiometry on
chromatin structure. Using indirect immunofluorescence and confocal
microscopy we found that Snf2h in ES cells is localized both in
euchromatin and to a lesser extent in heterochromatin. Its
expression is markedly reduced in Sn2h +/- cells. Chromatin of
Snf2h +/- ES cells exhibited multiple defects including decreased
amounts of heterochromatin and a significant decrease of
euchromatic marks including histone H3K79 and H4K16 acetylation. In
contrast, histone H3K9 acetylation and the level of another
chromatin remodeling ATPase, Brg-1, was not altered in Snf2h +/- ES
cells as compared to wild-type ES cells. Thus in ES cells Snf2h may
be involved in formation of both heterochromatin as well as
transcriptionaly active euchromatin. Our data support the role of
Snf2h in regulation of chromatin structure in leukemia, currently
tested using Snf2h heterozygous animals.
Abstract #4062 appears in Blood, Volume 110, issue 11, November 16,
2007
Keywords: Chromatin|Mouse Model|Embryonic Stem Cells
Disclosure: No relevant conflicts of interest to declare.
Session Info: Publication Only
Datum přednesení příspěvku: 8. 12. 2007