biology

Transcription coregulator

Transcription coregulator is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Transcription coregulator rather than just read about it. In short: In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that repress are known as corepressors.

Key takeaways

Transcription coregulator belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Transcription coregulator to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Transcription coregulator from memory before moving on to harder problems.

Reference excerpt

In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that repress are known as corepressors. The mechanism of action of transcription coregulators is to modify chromatin structure and thereby make the associated DNA more or less accessible to transcription. In humans several dozen to several hundred coregulators are known, depending on the level of confidence with which the characterisation of a protein as a coregulator can be made. One class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second ATP dependent class modifies the conformation of chromatin.

Histone acetyltransferases Nuclear DNA is normally tightly wrapped around histones rendering the DNA inaccessible to the general transcription machinery and hence this tight association prevents transcription of DNA. At physiological pH, the phosphate component of the DNA backbone is deprotonated which gives DNA a net negative charge. Histones are rich in lysine residues which at physiological pH are protonated and therefore positively charged. The electrostatic attraction between these opposite charges is largely responsible for the tight binding of DNA to histones. Many coactivator proteins have intrinsic histone acetyltransferase (HAT) catalytic activity or recruit other proteins with this activity to promoters. These HAT proteins are able to acetylate the amine group in the sidechain of histone lysine residues which makes lysine much less basic, not protonated at physiological pH, and therefore neutralizes the positive charges in the histone proteins. This charge neutralization weakens the binding of DNA to histones causing the DNA to unwind from the histone proteins and thereby significantly increases the rate of transcription of this DNA. Many corepressors can recruit histone deacetylase (HDAC) enzymes to promoters. These enzymes catalyze the hydrolysis of acetylated lysine residues restoring the positive charge to histone proteins and hence the tie between histone and DNA. PELP-1 can act as a transcriptional corepressor for transcription factors in the nuclear receptor family such as glucocorticoid receptors.

Nuclear receptor coactivators Nuclear receptors bind to coactivators in a ligand-dependent manner. A common feature of nuclear receptor coactivators is that they contain one or more LXXLL binding motifs (a contiguous sequence of 5 amino acids where L = leucine and X = any amino acid) referred to as NR (nuclear receptor) boxes. The LXXLL binding motifs have been shown by X-ray crystallography to bind to a groove on the surface of ligand binding domain of nuclear receptors. Examples include:

ARA (androgen receptor associated protein) ARA54 (RNF14) ARA55 (TGFB1I1) ARA70 (NCOA4) AIRE BCAS3 (breast carcinoma amplified sequence 3) CREB-binding protein CRTC (CREB regulated transcription coactivator) CRTC1 (CRTC1) CRTC2 (CRTC2) CRTC3 (CRTC3) CARM1 (coactivator-associated arginine methyltransferase 1) CARM1 Nuclear receptor coactivator (NCOA) NCOA1/SRC-1 (steroid receptor coactivator-1)/ NCOA1 NCOA2/GRIP1 (glucocorticoid receptor interacting protein 1)/ TIF2 (transcriptional intermediary factor 2) NCOA2 NCOA3/AIB1 (amplified in breast) NCOA3 NCOA4/ARA70 (androgen receptor associated protein 70) NCOA4 NCOA5 (NCOA5) NCOA6 (NCOA6) NCOA7 (NCOA7) p300 EP300 PCAF (p300/CBP associating factor) PCAF PGC1 (proliferator activated receptor gamma coactivator 1) PPARGC1A (PPARGC1A) PPARGC1B (PPARGC1B) PNRC (proline-rich nuclear receptor coactivator 1) PNRC1 (PNRC1) PNRC2 (PNRC2)

Nuclear receptor corepressors Corepressor proteins also bind to the surface of the ligand binding domain of nuclear receptors, but through a LXXXIXXX(I/L) motif of amino acids (where L = leucine, I = isoleucine and X = any amino acid). In addition, compressors bind preferentially to the apo (ligand free) form of the nuclear receptor (or possibly antagonist bound receptor).

CtBP 602618 SIN3A (associates with class II histone deacetylases) LCoR (ligand-dependent corepressor) Nuclear receptor CO-Repressor (NCOR) NCOR1 (NCOR1) NCOR2 (NCOR2)/SMRT (Silencing Mediator (co-repressor) for Retinoid and Thyroid-hormone receptors) (associates with histone deacetylase-3) Rb (retinoblastoma protein) RB1 (associates with histone deacetylase-1 and -2) RCOR (REST corepressor) RCOR1 (RCOR1) RCOR2 (RCOR2) RCOR3 (RCOR3) Sin3 SIN3A (SIN3A) SIN3B (SIN3B) TIF1 (transcriptional intermediary factor 1) TRIM24 Tripartite motif-containing 24 (TRIM24) TRIM28 Tripartite motif-containing 28 (TRIM28) TRIM33 Tripartite motif-containing 33 (TRIM33)

Dual function activator/repressors NSD1 (NSD1) PELP-1 (proline, glutamic acid and leucine rich protein 1) PELP1 RIP140 (receptor-interacting protein 140) NRIP1 YAP WWTR1 (TAZ)

ATP-dependent remodeling factors SWI/SNF family chromatin structure remodeling complex ISWI protein SMARCA1, SMARCA2

See also Coactivator (genetics) Corepressor (genetics) Nuclear receptor coregulators RNA polymerase control by chromatin structure Transcription Transcription factor TcoF-DB

References

External links "Nuclear Receptor Signaling Atlas (Receptors, Coactivators, Corepressors and Ligands)". The NURSA Consortium. Retrieved 2008-02-21. an NIH-funded research consortium and database; includes open-access PubMed-indexed journal, Nuclear Receptor Signaling

Worked examples

Example 1 — a first encounter with Transcription coregulator

Start with the simplest possible case. Write down what Transcription coregulator claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Transcription coregulator before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Transcription coregulator ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Transcription coregulator

In research: Transcription coregulator appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Transcription coregulator in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Transcription coregulator is common in secondary-school and first-year university syllabi. It links to neighbouring topics Gene expression, Transcription coregulators, so understanding it makes those chapters shorter.
In everyday life: Look for Transcription coregulator outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Transcription coregulator in 20 minutes

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Frequently asked questions

What is Transcription coregulator in simple terms?

Why does Transcription coregulator matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Transcription coregulator?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Transcription coregulator.