Repression of CTSG, ELANE and PRTN3-mediated histone H3 proteolytic cleavage promotes monocyte-to-macrophage differentiation.
Adolescent
Arthritis, Juvenile
/ blood
CRISPR-Cas Systems
/ genetics
Cathepsin G
/ genetics
Cell Differentiation
/ genetics
Cell Nucleus
/ metabolism
Child
Child, Preschool
Chromatin
/ metabolism
Enzyme Assays
Epigenesis, Genetic
/ immunology
Epigenomics
Female
Gene Knockout Techniques
Histones
/ metabolism
Humans
Jurkat Cells
Leukocyte Elastase
/ genetics
Leukocytes, Mononuclear
/ immunology
Macrophages
/ immunology
Male
Myeloblastin
/ genetics
Primary Cell Culture
Proteolysis
RNA-Seq
Recombinant Proteins
/ genetics
THP-1 Cells
Young Adult
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
27
12
2019
accepted:
05
04
2021
pubmed:
22
5
2021
medline:
22
7
2021
entrez:
21
5
2021
Statut:
ppublish
Résumé
Chromatin undergoes extensive reprogramming during immune cell differentiation. Here we report the repression of controlled histone H3 amino terminus proteolytic cleavage (H3ΔN) during monocyte-to-macrophage development. This abundant histone mark in human peripheral blood monocytes is catalyzed by neutrophil serine proteases (NSPs) cathepsin G, neutrophil elastase and proteinase 3. NSPs are repressed as monocytes mature into macrophages. Integrative epigenomic analysis reveals widespread H3ΔN distribution across the genome in a monocytic cell line and primary monocytes, which becomes largely undetectable in fully differentiated macrophages. H3ΔN is enriched at permissive chromatin and actively transcribed genes. Simultaneous NSP depletion in monocytic cells results in H3ΔN loss and further increase in chromatin accessibility, which likely primes the chromatin for gene expression reprogramming. Importantly, H3ΔN is reduced in monocytes from patients with systemic juvenile idiopathic arthritis, an autoinflammatory disease with prominent macrophage involvement. Overall, we uncover an epigenetic mechanism that primes the chromatin to facilitate macrophage development.
Identifiants
pubmed: 34017121
doi: 10.1038/s41590-021-00928-y
pii: 10.1038/s41590-021-00928-y
pmc: PMC8159908
mid: NIHMS1690831
doi:
Substances chimiques
Chromatin
0
Histones
0
Recombinant Proteins
0
CTSG protein, human
EC 3.4.21.20
Cathepsin G
EC 3.4.21.20
ELANE protein, human
EC 3.4.21.37
Leukocyte Elastase
EC 3.4.21.37
Myeloblastin
EC 3.4.21.76
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
711-722Subventions
Organisme : NIAMS NIH HHS
ID : K08 AR073339
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009302
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI125197
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR059049
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR069512
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI110491
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR070549
Pays : United States
Organisme : NIAMS NIH HHS
ID : K08 AR072075
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR061297
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR073201
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057229
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR070253
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM139569
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI109662
Pays : United States
Commentaires et corrections
Type : CommentIn
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