The Role of RING Finger Proteins in Chromatin Remodeling and Biological Functions

Figures & data

Figure 1. The nucleosome octameric structure consists of four core histone pairs: H2A, H2B, H3 and H4.

As E3 ubiquitin ligases, RING finger proteins ubiquitinate different Lys (K) sites of histones. The RING finger proteins corresponding to the ubiquitinated histone Lys sites are shown. Also see also Table 1 for references.

K: Lysine; Ub: Ubiquitin; Unknown: Lysine site remains unknown.

Table 1. RING finger proteins ubiquitinate different lysine sites of core histones.

RING finger protein	Histone lysine site	Ref.
	H2A
PRC1	H2AK119Ub	[17]
hPRC1L	H2AK119Ub	[18]
BCOR	H2AK119Ub	[19]
PCGF2/Mel-18-RING1B	H2AK119Ub	[20]
PCGF6	H2AK119Ub	[21]
KDM2B-PCGF1-RING1B	H2AK119Ub	[22,23]
BMI1-RING1A/B	H2AK118/119Ub	[24,25]
RNF8	H2AK13-15Ub	[26]
RNF168	H2AK13-15Ub	[26,27]
BRCA1/BARD1	H2AK124/127/129Ub	[28–36]
TRIM37	H2AK (unknown)	[7]
DZIP3 (hRUL138)	H2AK119Ub	[37]
FRRUC	H2AK119Ub	[23]
UBR1/UBR2	H2A (unknown)	[38,39]
PHF7	H2A (unknown)	[40]
DTX3L	H2AK (unknown)	[41]
HUWE1 (LASU1)	H2AK (unknown)	[42]
SHPRH	H2AK (unknown)	[43]
	H2B
RNF20/40	H2BK120	[9,10,44]
PHF6	H2BK120	[45]
MDM2	H2BK120	[46]
MSL1/MSL2	H2BK34	[47,48]
BRCA1/BARD1	H2BK (unknown)	[36]
DTX3L	H2BK (unknown)	[41]
HUWE1 (LASU1)	H2BK (unknown)	[42]
SHPRH	H2BK (unknown)	[43]
	H3
CLRC	H3K14	[49]
PHF7	H3K14	[50]
UHRF1	H3K18/23Ub	[11,51]
NEDD4	H3K23/36/37	[5]
CRL4	H3K79	[52]
BRCA1/BARD1	H3K (unknown)	[36]
HUWE1 (LASU1)	H3K (unknown)	[42]
MSL1-MSL2	H3K (unknown)	[47]
RNF4	H3K (unknown)	[53]
RNF138	H3K (unknown)	[54]
SHPRH	H3K (unknown)	[43]
CUL4-DDB-ROC1/RBX1	H3K (unknown)	[16]
	H4
Cul4A	H4K31	[55]
BBAP	H4K91	[56]
DTX3L	H4K (unknown)	[57]
BRCA1/BARD1	H4K (unknown)	[36]
HUWE1 (LASU1)	H4K (unknown)	[42]
MSL1-MSL2	H4K (unknown)	[47]
SHPRH	H4K (unknown)	[43]
CUL4-DDB-ROC1/RBX1	H4K (unknown)	[16]

Figure 2. The crosstalk between RING finger protein-mediated histone ubiquitination and other histone post-translational modifications, such as histone methylation and histone acetylation.

Different K sites of histones can be chemically modified by adding different small molecules. Ub and the corresponding RING finger proteins are shown in green, Me and the corresponding methyltransferases in orange, and Ac and the corresponding acetyltransferases in blue. Sharp arrows indicate facilitation; flat arrows indicate inhibition.

Ac: Acetyl; K: Lysine; Me: Methyl; Ub: Ubiquitination.

Table 2. RING finger proteins mediate the crosstalk between histone ubiquitination and histone methylation; the relationship between the interactions is also shown.

RING finger proteins	Ubiquitination	Methylation	Process of crosstalk	Ref.
PRC1	H2AK119	H3K27	PRC1 mediated H2AK119Ub promotes H3K27me3	[77,78]
PHF7	H2A	H3K4	PHF7 ubiquitinates H2A through binding H3K4me3/me2	[40]
MSL2	H2BK34	H3K4/79	MSL2 mediates H2BK34Ub, stimulating H3K4/K79 methylation	[47]
CLRC	H3K14	H3K9	H3K14 ubiquitination promotes H3K9 methylation	[49]
UHRF1	H3K18/23	H3K9	Uhrf1-dependent H3K18/K23Ub promotes H3K9 methylation	[11,51]
CRL4	H3K79	H3K9	CRL4 targets histone H3K79 and promotes H3K9 methylation	[52]
Cul4A	H4K31	H3K4/79	H4K31Ub by Cul4A Is necessary for methylation of H3K4/K79	[55]
BBAP	H4K91	H4K20	BBAP-mediated H4K91Ub promotes histone H4K20m	[56]

Table 3. RING finger proteins that mediate the crosstalk between histone ubiquitination and histone acetylation; the relationship between the interactions is also listed.

RING finger proteins	Ubiquitination	Acetylation	Process of crosstalk	Ref.
RNF168	H2AK15	H2BK120	RNF168-mediated H2AK15Ub inhibits H2BK120Ac.	[79]
PHF6	H2BK120	H2BK12	PHF6 mediates H2BK120Ub via H2BK12Ac recognition.	[45]
RNF8	H2B	H4K16	RNF8-mediated histone ubiquitination induces H4K16Ac.	[80]
NEDD4	H3K23/36/37	H3K9	NEDD4 ubiquitinates H3K23/36/37 and promotes H3K9Ac.	[5]

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