Differential expression and sex chromosome association of CHD3/4 and CHD5 during spermatogenesis.
ATP-dependent nucleosome remodelers of the CHD family play important roles in chromatin regulation during development and differentiation. The ubiquitously expressed CHD3 and CHD4 proteins are essential for stem cell function and serve to orchestrate gene expression in different developmental settings. By contrast, the closely related CHD5 is predominantly expressed in neural tissue and its role is believed to be restricted to neural differentiation. Indeed, loss of CHD5 contributes to neuroblastoma. In this study, we first demonstrate that CHD5 is a nucleosome-stimulated ATPase. We then compare CHD3/4 and CHD5 expression in mouse brain and show that CHD5 expression is restricted to a subset of cortical and hippocampal neurons whereas CHD3/4 expression is more widespread. We also uncover high levels of CHD5 expression in testis. CHD5 is transiently expressed in differentiating germ cells. Expression is first detected in nuclei of post-meiotic round spermatids, reaches a maximum in stage VIII spermatids and then falls to undetectable levels in stage IX spermatids. Surprisingly, CHD3/4 and CHD5 show complementary expression patterns during spermatogenesis with CHD3/4 levels progressively decreasing as CHD5 expression increases. In spermatocytes, CHD3/4 localizes to the pseudoautosomal region, the X centromeric region and then spreads into the XY body chromatin. In postmeiotic cells, CHD5 colocalises with macroH2A1.2 in association with centromeres and part of the Y chromosome. The subnuclear localisations of CHD4 and CHD5 suggest specific roles in regulation of sex chromosome chromatin and pericentromeric chromatin structure prior to the histone-protamine switch.
Institute for Molecular Biology and Tumor Research (IMT), Philipps Universität Marburg, Marburg, Germany.
Judith W
JW
Bergs
Institute for Molecular Biology and Tumor Research (IMT), Philipps Universität Marburg, Marburg, Germany.
Nina
N
Neuendorff
Department of Reproduction and Development, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Godfried
G
van der Heijden
Department of Reproduction and Development, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Evelyne
E
Wassenaar
Institut für Pathologie, Philipps Universität Marburg, Marburg, Germany.
Peter
P
Rexin
Institut für Zytobiologie und Zytopathologie, Philipps Universität Marburg, Marburg, Germany.
Hans-Peter
HP
Elsässer
Institut für Pathologie, Philipps Universität Marburg, Marburg, Germany.
Roland
R
Moll
Department of Reproduction and Development, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Willy M
WM
Baarends
Institute for Molecular Biology and Tumor Research (IMT), Philipps Universität Marburg, Marburg, Germany.
Alexander
A
Brehm
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000378:metabolism; D012730:Sex Chromosomes / Q000378:metabolism*; D013090:Spermatocytes / Q000166:cytology; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000378:metabolism
D002843:Chromatin; D011994:Recombinant Proteins; D000251:Adenosine Triphosphatases; C509277:Mi-2beta protein, mouse; D004265:DNA Helicases; C583981:Chd5 protein, mouse