Site-specific phosphorylation of histone H1 associated with cell cycle progression and transcription

Zheng, Yupeng

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https://hdl.handle.net/2142/16522 Copy

Description

Title

Site-specific phosphorylation of histone H1 associated with cell cycle progression and transcription

Author(s)

Zheng, Yupeng

Issue Date

2010-06-29T00:56:39Z

Director of Research (if dissertation) or Advisor (if thesis)

Mizzen, Craig A.

Doctoral Committee Chair(s)

Belmont, Andrew S.

Committee Member(s)

• Mizzen, Craig A.
• Bellini, Michel
• Jones, Peter L.
• Shapiro, David J.

Department of Study

Cell & Developmental Biology

Discipline

Cell and Developmental Biology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Date of Ingest

2010-06-29T00:56:39Z

Keyword(s)

• histone H1
• phosphorylation
• chromatin
• transcription
• nucleoli
• ribosomal RNA
• nuclear hormone receptors

Abstract

Histone H1 phosphorylation is thought to affect chromatin condensation and function, but few details are known about the impact of H1 variant-specific phosphorylation in higher eukaryotes. Using novel proteomic approaches, we directly demonstrate that specific sites in the two dominant H1 variants of HeLa S3 cells are phosphorylated either exclusively during mitosis or during both interphase and mitosis. Interphase H1 phosphorylation in HeLa S3 cells is abundant and remarkably hierarchical, contrary to evidence that sites are used fortuitously during the cell cycle. Analyses with antisera to individual H1.2 and H1.4 interphase phosphorylations reveal that they are distributed throughout nuclei but appear to be particularly enriched in nucleoli. Chromatin immunoprecipitation analyses reveal that interphase phosphorylated H1.4 is enriched at active rDNA promoters and is rapidly induced at steroid hormone response elements by hormone treatment. Our results imply that site-specific interphase H1 phosphorylation facilitates transcription by RNA polymerases I and II, and has an unanticipated function in ribosome biogenesis and the control of cell growth. In contrast to histone modifications enriched at gene regulatory regions, site-specific interphase H1 phosphorylation is enriched within the body and the regulatory elements of transcribed genes. Our data suggest CDK8 and CDK9, kinases with known association with the transcriptional machinery, as candidates that could account for this distribution of interphase H1 phosphorylation. Comparative analyses of H1 variant expression and phosphorylation in different human cell lines reveal that H1.3 is significantly less phosphorylated during interphase relative to other H1 variants in the cell lines tested. Analyses of the phosphorylation of site-specific H1 mutants ectopically expressed in human cells identified features of H1.3 that lead to its underphosphorylation. Together these results suggest that differences in interphase phosphorylation may contribute to the functional diversity of H1 variants.

Graduation Semester

2010-5

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http://hdl.handle.net/2142/16522

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Copyright 2010 by Yupeng Zheng. All rights reserved.

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