HDAC1 (histone deacetylase 1)

2017-08-01   Emanuely Silva Chrun , Filipe Modolo , Filipe Ivan Daniel 

Federal University of Santa Catarina, Florianopolis, Santa Catarina, emanuely.silva@gmail.com (ESC), Pathology Department, Federal University of Santa Catarina, Florianopolis, SC, Brazil. filipe.modolo@ufsc.br; filipe.daniel@ufsc.br (FM, FID)




HDAC1 is a Class I histone deacetylase (HDACs) encoded by this gene. HDACs remove acetyl group from amino-terminal tail of histone lysine recovering the positive charge of histone tail, permitting interactions between negatively charged DNA and histone protein, resulting in chromatin structure condensation which is associated with gene repression. Overexpression of this protein has been related to several malignancies, controlling tumour suppressor genes expression, feasible prognostics factor, and medications target. This paper propound data about HDAC1 gene, its protein encoded and function.



Located in chromosome 1. The entire HDAC1 gene is approximately 41,550 bases (start: 32,292,086 and end: 32,333,635 bp; orientation: Plus strand) and contains 14 exons.





HDAC1 is found mainly in the nucleus.


HDAC1 is an enzyme responsible for epigenetic alterations leading to modulation of chromatin structure and transcriptional regulation across lysine residues deacetylation on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (Fig. 1). It shows a role in cell cycle regulation and haematopoiesis (Dovey, et al. 2010). Deacetylation of TP53 by HDAC1 is a mechanism that participate of physiological activity of TP53 (Juan, et al. 2000 2000). It was also observed an important participation in cellular proliferation through direct regulation of CDKN1A (p21) gene (Zupkovitz, et al. 2010) 2010. HDAC2 is a HDAC1 homologue that, in part, compensates its loss and has redundant functions (Zupkovitz, et al. 2006 2006). These enzymes act through multiprotein co-repressor complexes such as: SIN3, NuRD, RCOR1 (CoREST) (Kelly and Cowley 2013).
Atlas Image
Fig. 1. Chromatin remodeling by histone acetylation changes. HATs catalyse the addition of acetyl groups turning histone tail charge to negative, leading to chromatin opening, while HDACs remove acetyl group from amino-terminal tail of histone lysine recovering its positive charge, closing the chromatin structure.


HDAC1 shares high homology between diverse species (Table 1).
Table 1. Comparative identity of human HDAC1 and its homologs in other species).



H. sapiens vs.SymbolProteinDNA
P. troglogytesHDAC199.899.4
P. troglogytesHDAC199.699.4
M. mulata LOC70844199.897.8
C. lupusHDAC199.294.1
B. taurusHDAC199.293.9
M. musculusHdac199.490.5
R. norvegicusHdac199.290.9
G. gallusHdac193.379.2
D. melanogaster Rpd382.172.2
A. gambiaeAgaP_AGAP00651183.172.8
C. eleganshda-369.563.5
S. cerevisiaeRPD364.860.3
K. lactisKLLA0E01981g65.461.2
E. gossypiiAGOS_AGR395W65.062.2
S. pombeclr664.563.2
M. oryzaeMGG_0585766.763.9
N. crassaNCU0082466.162.8
A. thalianaHD167.663.4
O. sativaOs02g0212490068.364.0
O. sativaOs06g058340069.265.4



A total of 60 substitution missense, 5 substitution nonsense, 29 substitution synonymous, no insertion frameshift, no deletions inframe, 2 deletion frameshift, none complex and none other mutations are reported in COSMIC (Catalogue of somatic mutations in cancer); it was found 110 mutated samples from a total of 29924 tested samples.

Implicated in

Entity name
Oral squamous cell carcinoma
HDAC1 overexpression was found in 55.10% of 49 mobile tongue squamous cell carcinoma evaluated whereas most of the cells from non-neoplastic epithelium presents negative immunoexpression for HDAC1 (Theocharis, et al. 2011). HDAC1 was overexpressed in 70% of lip squamous cell carcinoma (Fig.2) and in 77% of actinic cheilitis, with immunoexpression increasing in preneoplastic cases with severe epithelial dysplasia, and in neoplastic cases with poor differentiation (Chrun, et al. 2017).
Atlas Image
Fig. 2. Immunoexpression of HDAC1 in lip squamous cell carcinoma.
Entity name
Esophageal cancer
Comparing H4 acetylation and HDAC1 expression, it was observed hyperacetylation of H4 and decreased HDAC1 expression from esophageal normal tissue through esophageal carcinoma, suggesting that the equilibrium between HDAC and HAT is interrupted in this carcinoma (Toh, et al. 2003). Few cases of esophageal cancer were reported with HDAC1 overexpression when compared to normal esophageal mucosa (15%) (Nakagawa, et al. 2007). Esophageal adenocarcinoma also presented subexpression in majority of cases and was not associated to prognostic factor (Langer, et al. 2010).
Entity name
Thyroid cancer
HDAC1 immunoexpression was found in 99% of 47 thyroid malignances (papillary, follicular, medullary, and anaplastic thyroid carcinomas) and 23 benign thyroid tumors, with significant relation to tumor size, without difference in expression between malignant and benign thyroid tumors (Giaginis, et al. 2014). Nakagawa and collaborators reported immunoreactivity in all evaluated cases of papillary thyroid tumors (Nakagawa, et al. 2007).
Entity name
Gastric cancer
HDAC1 overexpression was detected by semi-quantitative RT-PCR, immunoblot analysis, and immunohistochemistry in gastric cancer tissues compared to its corresponding normal tissue (Choi, et al. 2001; Nakagawa, et al. 2007). Sudo and colleagues found association between HDAC expression and aggressive behavior of primary gastric cancer. In this study, HDAC1 overexpression was found by quantitative reverse transcription-PCR in gastric cancer tissue in 77% of the cases, with higher expression correlated to lymph vessel and vascular vessel permeations, advanced stage of the disease, and lymph node metastasis (Sudo, et al. 2011).
Entity name
Colorectal cancer
When comparing colorectal carcinoma cells and normal colonic mucosa by reverse transcription (RT)-PCR (Ishihama, et al. 2007) and immunohistochemistry (Nakagawa, et al. 2007) there was a greater HDAC1 expression in cancer than in normal colonic epithelium. Bernard and collaborators evaluated tissue microarray (TMA) with 254 colorectal adenocarcinomas samples and 50 normal colorectal tissues, showing no significant difference between normal and cancerous tissues, but suggested combination of higher HDAC expression and clinical outcomes for these patients (Benard, et al. 2015).
Entity name
Pancreatic cancer
HDAC1 with HDAC2 and SIN3A were recognized as complex silencing regulators of CDH1  (E-cadherin), thus involved in pancreatic adenocarcinoma metastasis (von Burstin, et al. 2009; Aghdassi, et al. 2012). Several HDACs were evaluated in (pNET): higher expression of HDAC1 was observed in high grade pNET and its expression showed positive correlation with mitotic (pHH3) and proliferation (Ki-67) index (Klieser, et al. 2017).
Entity name
Hodgkin`s lymphoma exhibited higher immunoexpression of HDAC1 when analysing 283 TMA (Adams, et al. 2010). In diffuse large B-cell lymphomas (DLBCL) HDAC1 immunoexpression was higher in comparison to reactive lymphoid hyperplasia which was correlated to cell proliferation index (Ki67) in the development of DLBCL, and associated with aggressiveness/poor survival of DLBCL patients (Min, et al. 2012). On the other hand, Lee and colleagues found faintly nuclear staining in few cases of 91 DLBCL samples submitted to immunohistochemistry (Lee, et al. 2014).
Entity name
Moreno and collaborators evaluated 94 cases of childhood acute lymphoblastic leukaemia (ALL) and found HDAC1 mRNA increased expression in T-cell ALL when compared to B-cell ALL. Yang et al. also found higher HDAC1 mRNA in ALL. (Moreno, et al. 2010). Quantitative real-time polymerase chain reaction also revealed higher HDAC1 expression in ALL (Yang, et al. 2015). Clinicopathological parameters indicated that overexpression of HDAC1 may be related to unfavourable prognosis of childhood ALL (Gruhn, et al. 2013).
Entity name
Lung cancer
HDAC1 is highly expressed in lung cancer (Nakagawa, et al. 2007). A correlation between HDAC1 mRNA and protein levels showed that HDAC1 gene expression might be involved with lung cancer progression (Sasaki, et al. 2004).
Entity name
Prostate cancer
Up-regulation of HDAC1 in prostate cancer compared to benign prostatic hyperplasia was demonstrated by immunohistochemistry (Patra, et al. 2001; Nakagawa, et al. 2007). Weichert and collaborators achieved immunohistochemistry for Class I HDAC isoforms in prostate carcinomas, showing HDAC1, HDAC2 and HDAC3 stronger expression accompanied by tumor cell proliferation raising (Weichert, et al. 2008). Overexpression of HDAC1 was also related to major increase of hormone refractory in prostate cancer and augmentation of proliferation (Halkidou, et al. 2004).
Entity name
Breast cancer
HDAC1 was evaluated in TMA from 238 patients with primary breast cancer and presented wide variation in positive imunnoexpression (Muller, et al. 2013). While Nakagawa (Nakagawa, et al. 2007) and Ververis (Ververis and Karagiannis 2012) showed higher expression of HDAC1 by immunohistochemistry and immunofluorescence respectively. Suzuki and colleagues detected a decrease in its expression from normal tissue through invasive ductal carcinoma, and from high grade through intermediate/low grade carcinoma (Suzuki, et al. 2009). Higher expression of HDAC1 was related to molecular subtypes (Luminal A, Luminal B, HER overexpressed, and triple-negative) and with improved overall survival (Seo, et al. 2014).
Entity name
Ovarian cancer
HDAC1 immunoexpression showed positive correlation with Ki-67 and inverse correlation with E-cadherin in 115 cases of ovarian tumors, suggesting an important participation of HDAC1 in cellular proliferation. Its overexpression was also associated with poor outcome (Hayashi, et al. 2010). Immunoreactivity for HDAC1 was sighted in 95% of cases evaluated, but without significant difference between histological subtypes of ovarian cancer (Nakagawa, et al. 2007). By immunohistochemistry and qRT-PCR, HDAC1 and DNMT3B revealed positive correlation in ovarian cancer; HDAC1 was highly expressed in comparison to normal ovarian tissue (Gu, et al. 2013). In a population-based cohort of 465 ovarian carcinomas, Weichert and collaborators observed higher level expression of HDAC1 and positive correlation with Ki67, indicating its participation in cell proliferation without significant interference in prognostic (Weichert 2009).
Entity name
Endometrial cancer
Strong HDAC1 immunoexpression was observed in endometrial stromal sarcoma, and it was suggested that this expression is linked to lower than 10 years disease free survival (Baek, et al. 2016). Endometrial adenocarcinomas compared to normal endometrium exhibited reduction in HDAC1 expression (Krusche, et al. 2005). However, in other research, endometrial carcinomas presented higher HDAC1 expression in comparison to normal endometrial tissue (Fakhry, et al. 2010). Weichert and colleagues evaluated 149 endometrial carcinomas and showed a higher level of HDAC1 expression that was positively correlated with cell proliferation indicator (Ki-67) and associated to 10 years survival decrease (Weichert 2009).


Pubmed IDLast YearTitleAuthors
204156002010Class I histone deacetylases 1, 2 and 3 are highly expressed in classical Hodgkin's lymphoma.Adams H et al
221475122012Recruitment of histone deacetylases HDAC1 and HDAC2 by the transcriptional repressor ZEB1 downregulates E-cadherin expression in pancreatic cancer.Aghdassi A et al
271271682016Immunohistochemical Characterization of Histone Deacetylase as a Potential Prognostic Marker and Therapeutic Target in Endometrial Stromal Sarcoma.Baek MH et al
253078642015Nuclear expression of histone deacetylases and their histone modifications predicts clinical outcome in colorectal cancer.Benard A et al
117496952001Expression profile of histone deacetylase 1 in gastric cancer tissues.Choi JH et al
281075822017Immunoexpression of HDAC1, HDAC2, and HAT1 in actinic cheilitis and lip squamous cell carcinoma.Chrun ES et al
204041882010Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation.Dovey OM et al
201788842010Immunohistochemical detection of histone deacetylases in endometrial carcinoma: involvement of histone deacetylase 2 in the proliferation of endometrial carcinoma cells.Fakhry H et al
238731022014Clinical significance of histone deacetylase (HDAC)-1, HDAC-2, HDAC-4, and HDAC-6 expression in human malignant and benign thyroid lesions.Giaginis C et al
239482812013The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia.Gruhn B et al
234200512013Investigation of the expression patterns and correlation of DNA methyltransferases and class I histone deacetylases in ovarian cancer tissues.Gu Y et al
150426182004Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer.Halkidou K et al
200498412010Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E-cadherin.Hayashi A et al
177207752007Expression of HDAC1 and CBP/p300 in human colorectal carcinomas.Ishihama K et al
107774772000Histone deacetylases specifically down-regulate p53-dependent gene activation.Juan LJ et al
236979332013The physiological roles of histone deacetylase (HDAC) 1 and 2: complex co-stars with multiple leading parts.Kelly RD et al
157705222005Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis.Krusche CA et al
209240322010Expression of class I histone deacetylases (HDAC1 and HDAC2) in oesophageal adenocarcinomas: an immunohistochemical study.Langer R et al
250768452014Expression of histone deacetylases in diffuse large B-cell lymphoma and its clinical significance.Lee SH et al
236275722013Differential expression of histone deacetylases HDAC1, 2 and 3 in human breast cancer--overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression.Müller BM et al
231099942012Expression of HAT1 and HDAC1, 2, 3 in Diffuse Large B-Cell Lymphomas, Peripheral T-Cell Lymphomas, and NK/T-Cell Lymphomas.Min SK et al
206364362010Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia.Moreno DA et al
177863342007Expression profile of class I histone deacetylases in human cancer tissues.Nakagawa M et al
115638532001Histone deacetylase and DNA methyltransferase in human prostate cancer.Patra SK et al
154746652004Histone deacetylase 1 mRNA expression in lung cancer.Sasaki H et al
255485792014Expression of Histone Deacetylases HDAC1, HDAC2, HDAC3, and HDAC6 in Invasive Ductal Carcinomas of the Breast.Seo J et al
217256042011Histone deacetylase 1 expression in gastric cancer.Sudo T et al
193838252009Protein acetylation and histone deacetylase expression associated with malignant breast cancer progression.Suzuki J et al
214573452011Histone deacetylase-1 and -2 expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival.Theocharis S et al
125792682003Histone H4 acetylation and histone deacetylase 1 expression in esophageal squamous cell carcinoma.Toh Y et al
223475202012An atlas of histone deacetylase expression in breast cancer: fluorescence methodology for comparative semi-quantitative analysis.Ververis K et al
191034712009HDAC expression and clinical prognosis in human malignancies.Weichert W et al
182127462008Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy.Weichert W et al
259444692015Analysis of class I and II histone deacetylase gene expression in human leukemia.Yang H et al
169401782006Negative and positive regulation of gene expression by mouse histone deacetylase 1.Zupkovitz G et al
193620902009E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex.von Burstin J et al

Other Information

Locus ID:

NCBI: 3065
MIM: 601241
HGNC: 4852
Ensembl: ENSG00000116478


dbSNP: 3065
ClinVar: 3065
TCGA: ENSG00000116478


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Cell cycleKEGGko04110
Notch signaling pathwayKEGGko04330
Huntington's diseaseKEGGko05016
Chronic myeloid leukemiaKEGGko05220
Cell cycleKEGGhsa04110
Notch signaling pathwayKEGGhsa04330
Huntington's diseaseKEGGhsa05016
Pathways in cancerKEGGhsa05200
Chronic myeloid leukemiaKEGGhsa05220
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Amphetamine addictionKEGGhsa05031
Amphetamine addictionKEGGko05031
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Thyroid hormone signaling pathwayKEGGhsa04919
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by NOTCH1 in CancerREACTOMER-HSA-2644603
Signaling by NOTCH1 PEST Domain Mutants in CancerREACTOMER-HSA-2644602
Constitutive Signaling by NOTCH1 PEST Domain MutantsREACTOMER-HSA-2644606
Signaling by NOTCH1 HD+PEST Domain Mutants in CancerREACTOMER-HSA-2894858
Constitutive Signaling by NOTCH1 HD+PEST Domain MutantsREACTOMER-HSA-2894862
Factors involved in megakaryocyte development and platelet productionREACTOMER-HSA-983231
Signal TransductionREACTOMER-HSA-162582
Signalling by NGFREACTOMER-HSA-166520
p75 NTR receptor-mediated signallingREACTOMER-HSA-193704
p75NTR negatively regulates cell cycle via SC1REACTOMER-HSA-193670
Signaling by TGF-beta Receptor ComplexREACTOMER-HSA-170834
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimerREACTOMER-HSA-2173793
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcriptionREACTOMER-HSA-2173796
Downregulation of SMAD2/3:SMAD4 transcriptional activityREACTOMER-HSA-2173795
Signaling by NOTCHREACTOMER-HSA-157118
Signaling by NOTCH1REACTOMER-HSA-1980143
NOTCH1 Intracellular Domain Regulates TranscriptionREACTOMER-HSA-2122947
Signaling by WntREACTOMER-HSA-195721
Degradation of beta-catenin by the destruction complexREACTOMER-HSA-195253
Repression of WNT target genesREACTOMER-HSA-4641265
TCF dependent signaling in response to WNTREACTOMER-HSA-201681
Formation of the beta-catenin:TCF transactivating complexREACTOMER-HSA-201722
Deactivation of the beta-catenin transactivating complexREACTOMER-HSA-3769402
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
RNA Polymerase I, RNA Polymerase III, and Mitochondrial TranscriptionREACTOMER-HSA-504046
RNA Polymerase I TranscriptionREACTOMER-HSA-73864
RNA Polymerase I Promoter ClearanceREACTOMER-HSA-73854
RNA Polymerase I Transcription InitiationREACTOMER-HSA-73762
Epigenetic regulation of gene expressionREACTOMER-HSA-212165
Negative epigenetic regulation of rRNA expressionREACTOMER-HSA-5250941
NoRC negatively regulates rRNA expressionREACTOMER-HSA-427413
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic G1-G1/S phasesREACTOMER-HSA-453279
G0 and Early G1REACTOMER-HSA-1538133
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
HDACs deacetylate histonesREACTOMER-HSA-3214815
Positive epigenetic regulation of rRNA expressionREACTOMER-HSA-5250913
Longevity regulating pathway - multiple speciesKEGGko04213
Longevity regulating pathway - multiple speciesKEGGhsa04213
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Activity through AcetylationREACTOMER-HSA-6804758
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expressionREACTOMER-HSA-427389

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA451846valproic acidChemicalPathwayassociated23407051


Pubmed IDYearTitleCitations
91501341997Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression.299
208024852010Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining.247
163199232006NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation.233
124263952002MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation.186
182127462008Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy.167
150426182004Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer.148
192525242009miR-449a targets HDAC-1 and induces growth arrest in prostate cancer.131
240369132013Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons.119
183471672008Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo.115
153618342004ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain.114


Emanuely Silva Chrun ; Filipe Modolo ; Filipe Ivan Daniel

HDAC1 (histone deacetylase 1)

Atlas Genet Cytogenet Oncol Haematol. 2017-08-01

Online version: http://atlasgeneticsoncology.org/gene/40802/hdac1-(histone-deacetylase-1)