Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis

Milstone, Zachary J.; Lawson, Grace; Trivedi, Chinmay M.

doi:10.1002/dvdy.24563

Cited by 17 publications

(16 citation statements)

References 83 publications

(132 reference statements)

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“…Tek-Cre ( 51 ), Cdh5-Cre ( 50 ), Lyve1-Cre ( 52 ), Pf4-iCre (codon-improved Cre recombinase) ( 53 ), and Gt(ROSA)26Sor ( 70 ) reporter mice were obtained from The Jackson Laboratory. Hdac1 fl/fl ( 71 ), Hdac2 fl/fl ( 72 ), and Hdac3 fl/fl ( 47 ) mice have been previously described.…”

Section: Methodsmentioning

confidence: 99%

Hdac3 regulates lymphovenous and lymphatic valve formation

Janardhan¹,

Milstone²,

Shin

et al. 2017

Journal of Clinical Investigation

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Lymphedema, the most common lymphatic anomaly, involves defective lymphatic valve development; yet the epigenetic modifiers underlying lymphatic valve morphogenesis remain elusive. Here, we showed that during mouse development, the histone-modifying enzyme histone deacetylase 3 (Hdac3) regulates the formation of both lymphovenous valves, which maintain the separation of the blood and lymphatic vascular systems, and the lymphatic valves. Endothelium-specific ablation of Hdac3 in mice led to blood-filled lymphatic vessels, edema, defective lymphovenous valve morphogenesis, improper lymphatic drainage, defective lymphatic valve maturation, and complete lethality. Hdac3-deficient lymphovenous valves and lymphatic vessels exhibited reduced expression of the transcription factor Gata2 and its target genes. In response to oscillatory shear stress, the transcription factors Tal1, Gata2, and Ets1/2 physically interacted with and recruited Hdac3 to the evolutionarily conserved E-box–GATA–ETS composite element of a Gata2 intragenic enhancer. In turn, Hdac3 recruited histone acetyltransferase Ep300 to form an enhanceosome complex that promoted Gata2 expression. Together, these results identify Hdac3 as a key epigenetic modifier that maintains blood-lymph separation and integrates both extrinsic forces and intrinsic cues to regulate lymphatic valve development.

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Section: Methodsmentioning

confidence: 99%

Hdac3 regulates lymphovenous and lymphatic valve formation

Janardhan¹,

Milstone²,

Shin

et al. 2017

Journal of Clinical Investigation

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“…E8.5 embryos were collected and sectioned at 8μm thickness for morphological analysis as previously described 26 . Hematoxylin- and eosin- staining was performed by de-paraffinizing sections in xylene, rehydrating slides through an ethanol gradient, staining for 30 s with 30% Harris modified hematoxylin and a 30 s counterstain with eosin Y.…”

Section: Methodsmentioning

confidence: 99%

“…Sections from E8.5 embryos were examined for proliferation and apoptosis defects by immunohistochemistry, following protocols described previously 26 . Briefly, sections were rehydrated through an ethanol gradient, followed by heat antigen retrieval (Buffer A, Electron Microscopy Sciences).…”

Section: Methodsmentioning

confidence: 99%

“…Immunostaining was conducted using the Vectastain Elite ABC and DAB Peroxidase Substrate kit according to manufacturer guidelines. Sections were incubated with H3S10P (1:100; Cell signaling, CSG 9706) or cleaved caspase 3 (1:100; Cell signaling, CSG 9661) biotinylated primary antibodies overnight at 4 °C 26 . For counterstaining, slides were rinsed and then incubated with 30% hematoxylin for 30 s after developing staining with 3,3′ diaminobenzimidine.…”

Section: Methodsmentioning

confidence: 99%

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TIP55, a splice isoform of the KAT5 acetyltransferase, is essential for developmental gene regulation and organogenesis

Acharya

Nera

Milstone

et al. 2018

Sci Rep

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Regulation of chromatin structure is critical for cell type-specific gene expression. Many chromatin regulatory complexes exist in several different forms, due to alternative splicing and differential incorporation of accessory subunits. However, in vivo studies often utilize mutations that eliminate multiple forms of complexes, preventing assessment of the specific roles of each. Here we examined the developmental roles of the TIP55 isoform of the KAT5 histone acetyltransferase. In contrast to the pre-implantation lethal phenotype of mice lacking all four Kat5 transcripts, mice specifically deficient for Tip55 die around embryonic day 11.5 (E11.5). Prior to developmental arrest, defects in heart and neural tube were evident in Tip55 mutant embryos. Specification of cardiac and neural cell fates appeared normal in Tip55 mutants. However, cell division and survival were impaired in heart and neural tube, respectively, revealing a role for TIP55 in cellular proliferation. Consistent with these findings, transcriptome profiling revealed perturbations in genes that function in multiple cell types and developmental pathways. These findings show that Tip55 is dispensable for the pre- and early post-implantation roles of Kat5, but is essential during organogenesis. Our results raise the possibility that isoform-specific functions of other chromatin regulatory proteins may play important roles in development.

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“…Nkx2.5 IRES-Cre (stock#: 024637), ROSA mT/mG (stock#: 007576), MHC MerCreMer (stock#: 005657), and R26R LacZ (stock#: 003474) were on October 11, 2020 http://advances.sciencemag.org/ Downloaded from obtained from the Jackson laboratory. Hdac1 Flox , Hdac2 Flox , and CMV Cre(ERT2) mice used in this study have been previously described (11). All animal protocols were approved by the University of Massachusetts Medical School Institutional Animal Care and Use Committee.…”

Section: Animalsmentioning

confidence: 99%

Histone deacetylases 1 and 2 silence cryptic transcription to promote mitochondrial function during cardiogenesis

et al. 2020

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Cryptic transcription occurs widely across the eukaryotic genome; however, its regulation during vertebrate development is not understood. Here, we show that two class I histone deacetylases, Hdac1 and Hdac2, silence cryptic transcription to promote mitochondrial function in developing murine hearts. Mice lacking Hdac1 and Hdac2 in heart exhibit defective developmental switch from anaerobic to mitochondrial oxidative phosphorylation (OXPHOS), severe defects in mitochondrial mass, mitochondrial function, and complete embryonic lethality. Hdac1/Hdac2 promotes the transition to OXPHOS by enforcing transcriptional fidelity of metabolic gene programs. Mechanistically, Hdac1/Hdac2 deacetylates histone residues including H3K23, H3K14, and H4K16 to suppress cryptic transcriptional initiation within the coding regions of actively transcribed metabolic genes. Thus, Hdac1/2-mediated epigenetic silencing of cryptic transcription is essential for mitochondrial function during early vertebrate development.

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Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis

Cited by 17 publications

References 83 publications

Hdac3 regulates lymphovenous and lymphatic valve formation

Hdac3 regulates lymphovenous and lymphatic valve formation

TIP55, a splice isoform of the KAT5 acetyltransferase, is essential for developmental gene regulation and organogenesis

Histone deacetylases 1 and 2 silence cryptic transcription to promote mitochondrial function during cardiogenesis

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