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Elevated embryonic expression of chromatin architectural protein HMGN5 alters higher order chromatin organization and leads to postnatal cardiac malfunction
Author(s) -
Rochman Mark,
Furusawa Takashi,
Bustin Michael
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.890.2
Subject(s) - chromatin , downregulation and upregulation , embryo , embryogenesis , microbiology and biotechnology , biology , embryonic stem cell , embryonic heart , transgene , andrology , endocrinology , medicine , genetics , gene
HMGN5 is a chromatin architectural protein that specifically binds to nucleosomes, unfolds chromatin and affects transcription. We report that HMGN5 is highly and ubiquitously expressed at preimplantation stages of embryonic development but is significantly down regulated in the embryo during implantation. To assess the importance of developmentally regulated HMGN5 expression, we generated conditional transgenic mice and induced exogenous HMGN5 expression either in the whole embryo or only in the embryonic heart. We found that upregulation of HMGN5 did not alter embryonic development and the mice were born normal. However, transgenic animals remained small in size and died within 2–3 months after birth. Pathological examination revealed significant alteration in the nuclear size and chromatin architecture of cardiomyocytes evident by reorganization of chromocenters. In addition, biochemical analysis showed upregulation of genes associated with cardiac stress. MRI tests indicated severe cardiac malfunction and hypertrophy. Our studies provide a direct link between global structural organization of chromatin fiber in the heart and a phenotypic outcome evident at the level of an entire organism.