Table 1 The overview of novel histone modifications

Crotonylation (Kcr)

P300/CBP; GNATs; MYSTs

HDAC3; SIRT1-3

YEATS domain; Af9/Taf14; ENL

Crotonyl-CoA; crotonate

2017

Activate transcription;¹⁵³ Regulate spermatogenesis;⁷ Regulate DNA damage response;⁴⁷⁶ Ensures accurate spindle positioning;⁴⁷⁷ Protect renal function;¹⁴ Ameliorate depression;¹⁶ Reactivate latent HIV;¹¹⁶ Facilitate telomere maintenance and differentiation of stem cells;¹¹⁵ Participates in the development of colon cancer;²¹³ Impacts the prognosis of prostate cancer;²²⁵ Regulates the process of spermatogenesis;¹¹⁴ Exacerbates major depressive disorder;^275,276,277 Plays a role in the occurrence of acute kidney injury and Immunoglobulin A nephropathy.^14,296

^{7,14,16,114,115,116,153,213,225,275,276,277,296,476,477}

Lactylation (Kla)

P300

HDAC1-3, SIRT1-3

NA

Lactyl-CoA, L-lactate

2019

Activate transcription⁴⁷⁸; Facilitate cell reprogramming⁴⁷⁸; Promote M1-M2 polarization^21,479; Foster lung fibrosis²⁹⁴; Accelerate ocular melanoma development^205,206; Influences on the growth of bladder cancer²⁰⁷; Enhancement of glycolysis in acute myeloid leukemia cells²⁰⁸; Affects the prognosis of colon²¹⁰、 breast cancer²¹⁰ and clear cell renal cell carcinoma²⁰⁹; Reflects the severity of critical illness and the presence of infection²⁴⁶; Modulates the transcription and latency of the HIV virus¹¹⁶; Contributes to the maintenance of myocardial contractile function⁴⁸⁰; Accelerates the progression of psoriasis.³⁰⁴

^{21,116,205,206,207,208,209,210,246,294,304,478,479,480}

Succinylation (Ksucc)

GNATs(GCN5);HAT1; P300/CBP

SIRT5; SIRT7

YEATS domain(SGAS1)

Succinyl-CoA; Succinate

2011

Activate transcription⁴⁸¹; Impair mitochondria respiration, mitophagy and metabolic flexibility⁴⁸²; Deter neuro filaments aggression in AD⁴⁸³; Exacerbate hypertrophic cardiomyopathy and

ischemia-perfusion injury⁴⁸⁴; Contributes to the progression of hepatocellular carcinoma, pancreatic cancer, and cholangiocarcinoma.²¹⁷

^{217,481,482,483,484}

Propionylation (Kpr)

P300/CBP; GNATs; MYSTs

SIRT1-3

Bromodomain; YEATS domain

Propionyl-CoA; Propionate

2007

Activate transcription¹³⁵; Facilitate protein aggregation in neurodegenerative diseases⁴⁸⁵;

^135,485

Butyrylation (Kbu)

P300/CBP; MYSTs

SIRT1-3

Bromodomain(BRD4,BPTF); CECR 2; AF1

Butyryl-CoA; Butyrate

2014

Activate transcription⁴⁸⁶; Promote spermatogenesis⁴⁶⁷;

^467,486

2-hydroxyisobutyrylation (Khib)

P300; MYSTs

HDAC1-3; SIRT1-3

NA

2-hydroxyisobutyryl-CoA

2016

Activate transcription⁸; Promote spermatogenesis⁸; Facilitates the onset of pancreatic cancer and oral squamous cell carcinoma^228,229

^8,228,229

2-hydroxybutyrylation (Khbb)

P300

SIRT3; HDAC1-3

NA

β-hydroxybutyryl-CoA

2016

Activate transcription²³; Promote memory development of CD8+Tmem cells⁴⁸⁷; Antagonize glomerulosclerosis induced by diabetes⁴⁸⁸; Alleviate depressive behaviors²⁹⁰; Exacerbates major depressive disorder.^275,276,277

^{23,275,276,277,290,487,488}