Histone acetylation in vivo at the osteocalcin locus is functionally linked to vitamin D-dependent, bone tissue-specific transcription

Jiali Shen, Martin Montecino, Jane B. Lian, Gary S. Stein, Andre J van Wijnen, Janet L. Stein

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The accessibility of regulatory elements in chromatin represents a principal rate-limiting parameter of gene transcription and is modulated by enzymatic transcriptional co-factors that alter the topology of chromatin or covalently modify histones (e.g. by acetylation). The bone-specific activation and 1,25-dihydroxyvitamin D3 enhancement of osteocalcin (OC) gene transcription are both functionally linked to modifications in nucleosomal organization. The initiation of tissue-specific basal transcription is accompanied by the induction of two DNase I hypersensitive sites, and this chromatin remodcling event requires binding of the key osteogenic factor RUNX2/CBFA1 to the OC promoter. Here, we analyzed the acetylation status of histones H3 and H4 when the OC gene is active (in osteoblastic ROS17/2.8 cells) or inactive (in fibroblastic ROS24/1 cells) using chromatin immunoprecipitation assays. We find that acetylated histone H3 and H4 proteins are associated with the OC promoter only when the gene is transcriptionally active and that the acetylation status is relatively uniform across the OC locus under basal conditions. Acetylation of H4 at the OC gene is selectively increased following vitamin D3 enhancement of OC transcription, with the most prominent changes occurring in the region between the vitamin D3 enhancer and basal promoter. Thus, our results suggest functional linkage of H3 and H4 acetylation in specific regions of the OC promoter to chromatin remodeling that accompanies tissue-specific transcriptional activation and vitamin D enhancement of OC gene expression. These findings provide mechanistic insights into bone-specific gene activation within a native genomic context in response to steroid hormone-related regulatory cues.

Original languageEnglish (US)
Pages (from-to)20284-20292
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number23
DOIs
StatePublished - Jun 7 2002
Externally publishedYes

Fingerprint

Acetylation
Osteocalcin
Transcription
Vitamin D
Histones
Bone
Tissue
Bone and Bones
Genes
Chromatin
Cholecalciferol
Chemical activation
Transcriptional Activation
Steroid hormones
Chromatin Assembly and Disassembly
Calcitriol
Chromatin Immunoprecipitation
Deoxyribonuclease I
Genetic Promoter Regions
Gene expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

Histone acetylation in vivo at the osteocalcin locus is functionally linked to vitamin D-dependent, bone tissue-specific transcription. / Shen, Jiali; Montecino, Martin; Lian, Jane B.; Stein, Gary S.; van Wijnen, Andre J; Stein, Janet L.

In: Journal of Biological Chemistry, Vol. 277, No. 23, 07.06.2002, p. 20284-20292.

Research output: Contribution to journalArticle

Shen, Jiali ; Montecino, Martin ; Lian, Jane B. ; Stein, Gary S. ; van Wijnen, Andre J ; Stein, Janet L. / Histone acetylation in vivo at the osteocalcin locus is functionally linked to vitamin D-dependent, bone tissue-specific transcription. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 23. pp. 20284-20292.
@article{26d92b08d4484efd99458a969378bf3e,
title = "Histone acetylation in vivo at the osteocalcin locus is functionally linked to vitamin D-dependent, bone tissue-specific transcription",
abstract = "The accessibility of regulatory elements in chromatin represents a principal rate-limiting parameter of gene transcription and is modulated by enzymatic transcriptional co-factors that alter the topology of chromatin or covalently modify histones (e.g. by acetylation). The bone-specific activation and 1,25-dihydroxyvitamin D3 enhancement of osteocalcin (OC) gene transcription are both functionally linked to modifications in nucleosomal organization. The initiation of tissue-specific basal transcription is accompanied by the induction of two DNase I hypersensitive sites, and this chromatin remodcling event requires binding of the key osteogenic factor RUNX2/CBFA1 to the OC promoter. Here, we analyzed the acetylation status of histones H3 and H4 when the OC gene is active (in osteoblastic ROS17/2.8 cells) or inactive (in fibroblastic ROS24/1 cells) using chromatin immunoprecipitation assays. We find that acetylated histone H3 and H4 proteins are associated with the OC promoter only when the gene is transcriptionally active and that the acetylation status is relatively uniform across the OC locus under basal conditions. Acetylation of H4 at the OC gene is selectively increased following vitamin D3 enhancement of OC transcription, with the most prominent changes occurring in the region between the vitamin D3 enhancer and basal promoter. Thus, our results suggest functional linkage of H3 and H4 acetylation in specific regions of the OC promoter to chromatin remodeling that accompanies tissue-specific transcriptional activation and vitamin D enhancement of OC gene expression. These findings provide mechanistic insights into bone-specific gene activation within a native genomic context in response to steroid hormone-related regulatory cues.",
author = "Jiali Shen and Martin Montecino and Lian, {Jane B.} and Stein, {Gary S.} and {van Wijnen}, {Andre J} and Stein, {Janet L.}",
year = "2002",
month = "6",
day = "7",
doi = "10.1074/jbc.M112440200",
language = "English (US)",
volume = "277",
pages = "20284--20292",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "23",

}

TY - JOUR

T1 - Histone acetylation in vivo at the osteocalcin locus is functionally linked to vitamin D-dependent, bone tissue-specific transcription

AU - Shen, Jiali

AU - Montecino, Martin

AU - Lian, Jane B.

AU - Stein, Gary S.

AU - van Wijnen, Andre J

AU - Stein, Janet L.

PY - 2002/6/7

Y1 - 2002/6/7

N2 - The accessibility of regulatory elements in chromatin represents a principal rate-limiting parameter of gene transcription and is modulated by enzymatic transcriptional co-factors that alter the topology of chromatin or covalently modify histones (e.g. by acetylation). The bone-specific activation and 1,25-dihydroxyvitamin D3 enhancement of osteocalcin (OC) gene transcription are both functionally linked to modifications in nucleosomal organization. The initiation of tissue-specific basal transcription is accompanied by the induction of two DNase I hypersensitive sites, and this chromatin remodcling event requires binding of the key osteogenic factor RUNX2/CBFA1 to the OC promoter. Here, we analyzed the acetylation status of histones H3 and H4 when the OC gene is active (in osteoblastic ROS17/2.8 cells) or inactive (in fibroblastic ROS24/1 cells) using chromatin immunoprecipitation assays. We find that acetylated histone H3 and H4 proteins are associated with the OC promoter only when the gene is transcriptionally active and that the acetylation status is relatively uniform across the OC locus under basal conditions. Acetylation of H4 at the OC gene is selectively increased following vitamin D3 enhancement of OC transcription, with the most prominent changes occurring in the region between the vitamin D3 enhancer and basal promoter. Thus, our results suggest functional linkage of H3 and H4 acetylation in specific regions of the OC promoter to chromatin remodeling that accompanies tissue-specific transcriptional activation and vitamin D enhancement of OC gene expression. These findings provide mechanistic insights into bone-specific gene activation within a native genomic context in response to steroid hormone-related regulatory cues.

AB - The accessibility of regulatory elements in chromatin represents a principal rate-limiting parameter of gene transcription and is modulated by enzymatic transcriptional co-factors that alter the topology of chromatin or covalently modify histones (e.g. by acetylation). The bone-specific activation and 1,25-dihydroxyvitamin D3 enhancement of osteocalcin (OC) gene transcription are both functionally linked to modifications in nucleosomal organization. The initiation of tissue-specific basal transcription is accompanied by the induction of two DNase I hypersensitive sites, and this chromatin remodcling event requires binding of the key osteogenic factor RUNX2/CBFA1 to the OC promoter. Here, we analyzed the acetylation status of histones H3 and H4 when the OC gene is active (in osteoblastic ROS17/2.8 cells) or inactive (in fibroblastic ROS24/1 cells) using chromatin immunoprecipitation assays. We find that acetylated histone H3 and H4 proteins are associated with the OC promoter only when the gene is transcriptionally active and that the acetylation status is relatively uniform across the OC locus under basal conditions. Acetylation of H4 at the OC gene is selectively increased following vitamin D3 enhancement of OC transcription, with the most prominent changes occurring in the region between the vitamin D3 enhancer and basal promoter. Thus, our results suggest functional linkage of H3 and H4 acetylation in specific regions of the OC promoter to chromatin remodeling that accompanies tissue-specific transcriptional activation and vitamin D enhancement of OC gene expression. These findings provide mechanistic insights into bone-specific gene activation within a native genomic context in response to steroid hormone-related regulatory cues.

UR - http://www.scopus.com/inward/record.url?scp=0037036448&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037036448&partnerID=8YFLogxK

U2 - 10.1074/jbc.M112440200

DO - 10.1074/jbc.M112440200

M3 - Article

VL - 277

SP - 20284

EP - 20292

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 23

ER -