Promoter ChIP-chip analysis in mouse testis reveals Y chromosome occupancy by HSF2.
The mammalian Y chromosome is essential for spermatogenesis, which is characterized by sperm cell differentiation and chromatin condensation for acquisition of correct shape of the sperm. Deletions of the male-specific region of the mouse Y chromosome long arm (MSYq), harboring multiple copies of a few genes, lead to sperm head defects and impaired fertility. Using chromatin immunoprecipitation on promoter microarray (ChIP-chip) on mouse testis, we found a striking in vivo MSYq occupancy by heat shock factor 2 (HSF2), a transcription factor involved in spermatogenesis. HSF2 was also found to regulate the transcription of MSYq resident genes, whose transcriptional regulation has been unknown. Importantly, disruption of Hsf2 caused a similar phenotype as the 2/3 deletion of MSYq, i.e., altered expression of the multicopy genes and increased mild sperm head abnormalities. Consequently, aberrant levels of chromatin packing proteins and more frequent DNA fragmentation were detected, implying that HSF2 is required for correct chromatin organization in the sperm. Our findings define a physiological role for HSF2 in the regulation of MSYq resident genes and the quality of sperm.
Akerfelt
Malin
M
Turku Centre for Biotechnology, University of Turku and Abo Akademi University, FIN-20520 Turku, Finland.
Henriksson
Eva
E
Laiho
Asta
A
Vihervaara
Anniina
A
Rautoma
Karoliina
K
Kotaja
Noora
N
Sistonen
Lea
L
D000818:Animals; D048430:Cell Shape / Q000502:physiology; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation / Q000379:methods; D002872:Chromosome Deletion; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism*; D053938:DNA Fragmentation; D005298:Fertility / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D013077:Sperm Head / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D014998:Y Chromosome / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D006360:Heat-Shock Proteins; C531390:Hsf2 protein, mouse; D014157:Transcription Factors