TY - JOUR
T1 - Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation
AU - Fan, Yuhong
AU - Nikitina, Tatiana
AU - Zhao, Jie
AU - Fleury, Tomara J.
AU - Bhattacharyya, Riddhi
AU - Bouhassira, Eric E.
AU - Stein, Arnold
AU - Woodcock, Christopher L.
AU - Skoultchi, Arthur I.
N1 - Funding Information:
This work was supported by NIH grants CA79057 (A.I.S.), GM43786 (C.L.W.), and GM62857 (A.S.). The authors wish to thank the AECOM Microarray Facility, the AECOM Laboratory of Macromolecular Analysis, and Christina Lowes at the AECOM Pyrosequencing Facility. We thank Dr. En Li for generously providing the pMO probe and Dnmt1 −/− ES cell DNA and Dr. Michael Bustin for the generous gift of the affinity-purified anti-H1 antiserum. We thank Yamini Dalal for contributions toward the NRL determinations at the ADA locus, and we also thank Xing Han for technical assistance and Kevin Choe for helpful discussion. We also gratefully acknowledge technical advice from Dr. Winfried Edelmann, Elena Avdievich, and Diana Lin on ES cell-line derivation.
PY - 2005/12/29
Y1 - 2005/12/29
N2 - Linker histone H1 plays an important role in chromatin folding in vitro. To study the role of H1 in vivo, mouse embryonic stem cells null for three H1 genes were derived and were found to have 50% of the normal level of H1. H1 depletion caused dramatic chromatin structure changes, including decreased global nucleosome spacing, reduced local chromatin compaction, and decreases in certain core histone modifications. Surprisingly, however, microarray analysis revealed that expression of only a small number of genes is affected. Many of the affected genes are imprinted or are on the X chromosome and are therefore normally regulated by DNA methylation. Although global DNA methylation is not changed, methylation of specific CpGs within the regulatory regions of some of the H1 regulated genes is reduced. These results indicate that linker histones can participate in epigenetic regulation of gene expression by contributing to the maintenance or establishment of specific DNA methylation patterns.
AB - Linker histone H1 plays an important role in chromatin folding in vitro. To study the role of H1 in vivo, mouse embryonic stem cells null for three H1 genes were derived and were found to have 50% of the normal level of H1. H1 depletion caused dramatic chromatin structure changes, including decreased global nucleosome spacing, reduced local chromatin compaction, and decreases in certain core histone modifications. Surprisingly, however, microarray analysis revealed that expression of only a small number of genes is affected. Many of the affected genes are imprinted or are on the X chromosome and are therefore normally regulated by DNA methylation. Although global DNA methylation is not changed, methylation of specific CpGs within the regulatory regions of some of the H1 regulated genes is reduced. These results indicate that linker histones can participate in epigenetic regulation of gene expression by contributing to the maintenance or establishment of specific DNA methylation patterns.
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U2 - 10.1016/j.cell.2005.10.028
DO - 10.1016/j.cell.2005.10.028
M3 - Article
C2 - 16377562
AN - SCOPUS:29244449333
SN - 0092-8674
VL - 123
SP - 1199
EP - 1212
JO - Cell
JF - Cell
IS - 7
ER -